Pesticidal compositions

ABSTRACT

This document discloses molecules having the following formula (“Formula I”):

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. provisional application61/175,659 filed on 5 May 2009. The entire content of this provisionalapplication is hereby incorporated by reference into this application.

FIELD OF THE INVENTION

The invention disclosed in this document is related to the field ofprocesses to produce molecules that are useful as pesticides (e.g.,acaricides, insecticides, molluscicides, and nematicides), suchmolecules, and processes of using such molecules to control pests.

BACKGROUND OF THE INVENTION

Pests cause millions of human deaths around the world each year.Furthermore, there are more than ten thousand species of pests thatcause losses in agriculture. The world-wide agricultural losses amountto billions of U.S. dollars each year.

Termites cause damage to all kinds of private and public structures. Theworld-wide termite damage losses amount to billions of U.S. dollars eachyear.

Stored food pests eat and adulterate stored food. The world-wide storedfood losses amount to billions of U.S. dollars each year, but moreimportantly, deprive people of needed food.

There is an acute need for new pesticides. Certain pests are developingresistance to pesticides in current use. Hundreds of pest species areresistant to one or more pesticides. The development of resistance tosome of the older pesticides, such as DDT, the carbamates, and theorganophosphates, is well known. But resistance has even developed tosome of the newer pesticides.

Therefore, for many reasons, including the above reasons, a need existsfor new pesticides.

Definitions

The examples given in the definitions are generally non-exhaustive andmust not be construed as limiting the invention disclosed in thisdocument. It is understood that a substituent should comply withchemical bonding rules and steric compatibility constraints in relationto the particular molecule to which it is attached.

“Acaricide Group” is defined under the heading “ACARICIDES”.

“AI Group” is defined after the place in this document where the“Herbicide Group” is defined.

“alkenyl” means an acyclic, unsaturated (at least one carbon-carbondouble bond), branched or unbranched, substituent consisting of carbonand hydrogen, for example, vinyl, allyl, butenyl, pentenyl, hexenyl,heptenyl, octenyl, nonenyl, and decenyl.

“alkenyloxy” means an alkenyl further consisting of a carbon-oxygensingle bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy,heptenyloxy, octenyloxy, nonenyloxy, and decenyloxy.

“alkoxy” means an alkyl further consisting of a carbon-oxygen singlebond, for example, methoxy, ethoxy, propoxy, isopropoxy, 1-butoxy,2-butoxy, isobutoxy, tert-butoxy, pentoxy, 2-methylbutoxy,1,1-dimethylpropoxy, hexoxy, heptoxy, octoxy, nonoxy, and decoxy.

“alkyl” means an acyclic, saturated, branched or unbranched, substituentconsisting of carbon and hydrogen, for example, methyl, ethyl, propyl,isopropyl, 1-butyl, 2-butyl, isobutyl, tert-butyl, pentyl,2-methylbutyl, 1,1-dimethylpropyl, hexyl, heptyl, octyl, nonyl, anddecyl.

“alkynyl” means an acyclic, unsaturated (at least one carbon-carbontriple bond, and any double bonds), branched or unbranched, substituentconsisting of carbon and hydrogen, for example, ethynyl, propargyl,butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, and decynyl.

“alkynyloxy” means an alkynyl further consisting of a carbon-oxygensingle bond, for example, pentynyloxy, hexynyloxy, heptynyloxy,octynyloxy, nonynyloxy, and decynyloxy.

“aryl” means a cyclic, aromatic substituent consisting of hydrogen andcarbon, for example, phenyl, naphthyl, and biphenyl.

“cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at leastone carbon-carbon double bond) substituent consisting of carbon andhydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, cyclodecenyl, norbornenyl,bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl, andoctahydronaphthyl.

“cycloalkenyloxy” means a cycloalkenyl further consisting of acarbon-oxygen single bond, for example, cyclobutenyloxy,cyclopentenyloxy, cyclohexenyloxy, cycloheptenyloxy, cyclooctenyloxy,cyclodecenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

“cycloalkyl” means a monocyclic or polycyclic, saturated substituentconsisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, norbornyl,bicyclo[2.2.2]octyl, and decahydronaphthyl.

“cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygensingle bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy,cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, cyclodecyloxy,norbornyloxy, and bicyclo[2.2.2]octyloxy.

“cyclohaloalkyl” means a monocyclic or polycyclic, saturated substituentconsisting of carbon halo, and hydrogen, for example,1-chlorocyclopropyl, 1-chlorocyclobutyl, and 1-dichlorocyclopentyl.

“Fungicide Group” is defined under the heading “FUNGICIDES”.

“halo” means fluoro, chloro, bromo, and iodo.

“haloalkyl” means an alkyl further consisting of, from one to themaximum possible number of, identical or different, halos, for example,fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl,2-fluoroethyl, 2,2,2-trifluoroethyl, chloromethyl, trichloromethyl, and1,1,2,2-tetrafluoroethyl.

“Herbicide Group” is defined under the heading “HERBICIDES.”

“heterocyclyl” means a cyclic substituent that may be fully saturated,partially unsaturated, or fully unsaturated, where the cyclic structurecontains at least one carbon and at least one heteroatom, where saidheteroatom is nitrogen, sulfur, or oxygen, for example, benzofuranyl,benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl,benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl,isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, 1,3,4-oxadiazolyl,oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl,pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl,quinoxalinyl, 1,2,3,4-tetrazolyl, thiazolinyl, thiazolyl, thienyl,1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl, and1,2,4-triazolyl.

“Insecticide Group” is defined under the heading “INSECTICIDES”.

“Nematicide Group” is defined under the heading “NEMATICIDES”.

“Synergist Group” is defined under the heading “SYNERGISTIC MIXTURES ANDSYNERGISTS”.

DETAILED DESCRIPTION OF THE INVENTION

This document discloses molecules having the following formula (“FormulaI”):

wherein:

-   (a) X is N or CR8;-   (b) R1 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀    heterocyclyl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂,    N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R1, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl,(each of which that can be substituted, may optionally be substitutedwith R9);

-   (c) R2 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀    heterocyclyl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂,    N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R2, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl,(each of which that can be substituted, may optionally be substitutedwith R9);

-   (d) R3 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀    heterocyclyl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂,    N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R3, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl,(each of which that can be substituted, may optionally be substitutedwith R9);

-   (e) R4 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀    heterocyclyl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂,    N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R4, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl,(each of which that can be substituted, may optionally be substitutedwith R9);

-   (f) R5 is H, substituted or unsubstituted C₁-C₆ alkyl, substituted    or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₁-C₆    alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted    or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted    C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl,    substituted or unsubstituted C₁-C₂₀ heterocyclyl, OR9, C(═X1)R9,    C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂, N(R9)C(═X1)R9, SR9, S(O)_(n)OR9,    R9S(O)_(n)R9, C₁-C₆ alkyl C₆-C₂₀ aryl (wherein the alkyl and aryl    can independently be substituted or unsubstituted), C(═X2)R9,    C(═X1)X2R9, R9X2C(═X1)R9, R9X2R9, C(═O)(C₁-C₆ alkyl)S(O)_(n)(C₁-C₆    alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), (C₁-C₆    alkyl)OC(═O)(C₆-C₂₀ aryl), (C₁-C₆ alkyl)OC(═O)(C₁-C₆ alkyl), C₁-C₆    alkyl-(C₃-C₁₀) cyclohaloalkyl), or (C₁-C₆ alkenyl)C(═O)O(C₁-C₆    alkyl), or R9X2C(═X1)X2R9;

wherein each said R5, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl,R9 aryl (each of which that can be substituted, may optionally besubstituted with R9)

optionally R5 and R7 can be connected in a cyclic arrangement, whereoptionally such arrangement can have one or more heteroatoms selectedfrom O, S, or, N, in the cyclic structure connecting R5 and R7;

-   (g) R6 is O, S, NR9, or NOR9;-   (h) R7 is substituted or unsubstituted C₁-C₆ alkyl, substituted or    unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₁-C₆    alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted    or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted    C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl,    substituted or unsubstituted C₁-C₂₀ heterocyclyl, OR9,    OR9S(O)_(n)R9, C(═X1)R9, C(═X1)OR9, R9C(═X1)OR9, R9X2C(═X1)R9X2R9,    C(═X1)N(R9)₂, N(R9)₂, N(R9)(R9S(O)_(n)R9), N(R9)C(═X1)R9, SR9,    S(O)_(n)OR9, R9S(O)_(n)R9, C₁-C₆alkylOC(═O)C₁-C₆alkyl, OC₁-C₆ alkyl    C₁-C₂₀ heterocyclyl, C₁-C₆alkylC₁-C₂₀ heterocyclyl, C₁-C₆,    alkylS(═N—CN)(C₁-C₆alkyl), C₁-C₆alkylS(O)(═N—CN)(C₁-C₆alkyl),    C₁-C₆alkylS(O)_(n)(C₁-C₆alkylC₁-C₂₀heterocyclyl),    C₁-C₆alkylS(O)(═N—CN)(C₁-C₆ alkyl-C₁-C₂₀heterocyclyl),    C₁-C₆alkylNH(C(═O)OC₁-C₆ alkyl), C₁-C₆ alkylC(═O)OC₁-C₆ alkyl,    C₁-C₆alkyl(C₆-C₂₀aryl)NH(C(═O)OC₁-C₆alkyl), C₁-C₆alkyl(S—C₁-C₆    alkyl)NH(C(═O)OC₁-C₆alkyl),    C₁-C₆alkyl(S—C₁-C₆alkyl-C₆-C₂₀aryl)NH(C(═O)OC₁-C₆alkyl), C₁-C₆    alkyl(NHC(═O)OC₁-C₆alkylC₆-C₂₀ aryl)NH(C(═O)OC₁-C₆alkyl),    C₁-C₆alkyl(OC₁-C₆alkylC₆-C₂₀aryl)NH(C(═O)OC₁-C₆alkyl),    C₁-C₆alkylN(C₁-C₆alkyl)(C(═O)OC₁-C₆alkyl), C₁-C₆alkylNH(C₁-C₆alkyl),    C₆-C₂₀arylSC₁-C₆halo alkyl, C₁-C₆alkyl-N(C₁-C₆ alkyl)    (C(═O)C₁-C₆alkylC₆-C₂₀aryl), C₁-C₆alkylN(C₁-C₆alkyl)(C₁-C₆alkyl),    C₁-C₆alkylN(C₁-C₆alkyl)(S(O)_(n)C₁-C₆alkyl), C₁-C₆ alkylN(C₁-C₆    alkyl)(S(O)_(n)C₁-C₆alkenylC₆-C₂₀aryl), C₁-C₆alkylN(C₁-C₆    alkyl)(C(═O)C₁-C₂₀ heterocyclyl),    C₁-C₆alkylN(C₁-C₆alkyl)(C(═O)OC₁-C₆ alkylC₆-C₂₀aryl), NH(C₁-C₆    alkylS(O)_(n)C₁-C₆alkyl), NH(C₁-C₆ alkylS(O)_(n)C₆-C₂₀ aryl),    C₁-C₆alkyl(S(O)_(n)C₁-C₆ alkyl)(C(═O)C₁-C₆alkylS(O)_(n)(C₁-C₆    alkyl), or R9S(O)_(n)(NZ)R9,

wherein each said R7, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl,(each of which that can be substituted, may optionally be substitutedwith R9), C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, ═X2, N(R9)₂, S(═X2)_(n)R9,R9S(O)_(n)R9, S(O)_(n)N(R9)₂;

-   (i) R8 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀    heterocyclyl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂,    N(R9)C(═X1)R9, SR9, S(O)_(n)R9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R8, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl,(each of which that can be substituted, may optionally be substitutedwith R9);

-   (j) R9 (each independently) is H, CN, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀    heterocyclyl, S(O)_(n)C₁-C₆ alkyl, N(C₁-C₆alkyl)₂,

wherein each said R9, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OC₁-C₆ alkyl, OC₁-C₆ haloalkyl, S(O)_(n)C₁-C₆alkyl,S(O)_(n)OC₁-C₆ alkyl, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl;

-   (k) n is 0, 1, or 2;-   (l) X1 is (each independently) O or S;-   (m) X2 is (each independently) O, S, ═NR9, or ═NOR9; and-   (n) Z is CN, NO₂, C₁-C₆ alkyl(R9), C(═X1)N(R9)₂.

In another embodiment of this invention:

-   (a) X is N or CR8;-   (b) R1 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂,    N(R9)₂, N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R1, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, or C₆-C₂₀ aryl, (each of which thatcan be substituted, may optionally be substituted with R9);

-   (c) R2 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂,    N(R9)₂, N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R2, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, or C₆-C₂₀ aryl, (each of which thatcan be substituted, may optionally be substituted with R9);

-   (d) R3 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂,    N(R9)₂, N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R3, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, or C₆-C₂₀ aryl, (each of which thatcan be substituted, may optionally be substituted with R9);

-   (e) R4 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂,    N(R9)₂, N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R4, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, or C₆-C₂₀ aryl, (each of which thatcan be substituted, may optionally be substituted with R9);

-   (f) R5 is H, substituted or unsubstituted C₁-C₆ alkyl, substituted    or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₁-C₆    alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted    or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted    C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, OR9,    C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂, N(R9)C(═X1)R9, SR9,    S(O)_(n)OR9, R9S(O)_(n)R9, C₁-C₆ alkyl C₆-C₂₀ aryl (wherein the    alkyl and aryl can independently be substituted or unsubstituted),    C(═X2)R9, C(═X1)X2R9, R9X2C(═X1)R9, R9X2R9, or R9X2C(═X1)X2R9;

wherein each said R5, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, or C₆-C₂₀ aryl, R9 aryl (each ofwhich that can be substituted, may optionally be substituted with R9)

optionally R5 and R7 can be connected in a cyclic arrangement, whereoptionally such arrangement can have one or more heteroatoms selectedfrom O, S, or, N, in the cyclic structure connecting R5 and R7;

-   (g) R6 is O, S, NR9, or NOR9;-   (h) R7 is substituted or unsubstituted C₁-C₆ alkyl, substituted or    unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₁-C₆    alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted    or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted    C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, OR9,    OR9S(O)_(n)R9, C(═X1)R9, C(═X1)OR9, R9C(═X1)OR9, R9X2C(═X1)R9X2R9,    C(═X1)N(R9)₂, N(R9)₂, N(R9)(R9S(O)_(n)R9), N(R9)C(═X1)R9, SR9,    S(O)_(n)OR9, R9S(O)_(n)R9, or R9S(O)_(n)(NZ)R9,

wherein each said R7, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, or C₆-C₂₀ aryl, (each of which thatcan be substituted, may optionally be substituted with R9)

-   (i) R8 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂,    N(R9)₂, N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

wherein each said R8, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OR9, S(O)_(n)OR9, or C₆-C₂₀ aryl (each of which thatcan be substituted, may optionally be substituted with R9);

-   (j) R9 (each independently) is H, CN, substituted or unsubstituted    C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted    or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆    alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl,    substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or    unsubstituted C₆-C₂₀ aryl,

wherein each said R9, which is substituted, has one or more substituentsselected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₁-C₆haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy,C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀halocycloalkenyl, OC₁-C₆ alkyl, OC₁-C₆ haloalkyl, S(O)_(n)OC₁-C₆ alkyl,C₆-C₂₀ aryl;

-   (k) n is 0, 1, or 2;-   (l) X1 is (each independently) O or S;-   (m) X2 is (each independently) O, S, ═NR9, or ═NOR9; and-   (n) Z is CN, NO₂, C₁-C₆ alkyl(R9), C(═X1)N(R9)₂.

In another embodiment of the invention X is preferably CR8.

In another embodiment of this invention R1 is preferably H, F, Cl, orC₁-C₆ alkoxy.

In another embodiment of this invention R1 is more preferably H, F, Cl,or OCH₃.

In another embodiment of this invention R1 is even more preferably H,

In another embodiment of this invention R2 and R3 are preferably H.

In another embodiment of this invention R4 is H, F, Cl, Br, I, CN, C₁-C₆alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₆-C₂₀ aryl, C(═O)O(C₁-C₆ alkyl),or S(C₁-C₆ alkyl).

In another embodiment of this invention R4 is preferably H, C₁, CF₃,CH₃, CH₂CH₃, CH(CH₃)₂, SCH₃, C(═O)OCH₂CH₃, or phenyl.

In another embodiment of this invention R4 is more preferably H, Cl, orCH₃.

In another embodiment of this invention R4 is even more preferably Cl.

In another embodiment of this invention R5 is preferably C(═O)(C₁-C₆alkyl)S(O)_(n)(C₁-C₆ alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl),(C₁-C₆ alkyl)OC(═O)(C₆-C₂₀ aryl), (C₁-C₆ alkyl)OC(═O)(C₁-C₆ alkyl),C₁-C₆ alkyl-(C₃-C₁₀ cyclohaloalkyl), or (C₁-C₆ alkenyl)C(═O)O(C₁-C₆alkyl).

In another embodiment of this invention R5 is more preferablyC(═O)CH(CH₃)CH₂SCH₃, C(═O)CH₂CH₂SCH₃, C(═O)CH₂CH₂C(O)OCH₃,C(═O)C(CH₃)₂CH₂SCH₃, CH₂C(═O)-phenyl, CH₂C(═O)CH₂CH₂CH₃,C(═O)CH(CH₃)SCH₃, CH₂(2,2-difluorocyclopropyl), or CH₂CH═CHC(═O)OCH₃.

In another embodiment of this invention R5 is preferably H, C₁-C₆ alkyl,C₁-C₆ alkyl-C₆-C₂₀ aryl, C₂-C₆ alkenyl, C(═O)(C₁-C₆ alkyl), (C₁-C₆alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl)(C₆-C₂₀ aryl),C(═O)O(C₁-C₆ alkyl), C(═O)(C₂-C₆ alkenyl), C₁-C₆ alkyl(substitutedC₆-C₂₀ aryl), C₁-C₆ haloalkyl, C₁-C₆ alkyl-(C₃-C₁₀ cycloalkyl), (C₃-C₁₀cycloalkyl)O(C₁-C₆ alkyl) or (C₁-C₆ alkyl)S(O)_(n)(C₁-C₆ alkyl).

In another embodiment of this invention R5 is more preferably H, CH₃,CH₂CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, CH₂-phenyl, C(═O)CH(CH₃)₂, C(═O)OC(CH₃)₃,C(═O)CH₃, CH₂OCH₃, C(O)CH═CH₂, CH₂-phenyl-OCH₃, CH₂OCH₂-phenyl,CH₂CH₂CH₃, CH₂CH₂F, CH₂CH═CH₂, CH₂CH₂OCH₃, CH₂cyclopropyl, CH₂CH═CHCH₃,cyclopropyl-O—CH₂CH₃, CH₂CH₂SCH₃, or CH₂CH₂S(O)₂CH₃.

In another embodiment of this invention R5 is even more preferably H,CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH(CH₃)₂, or CH₂CH₂CH₃.

In another embodiment of this invention R6 is preferably O, S, orN(C₁-C₆ alkyl).

In another embodiment of this invention R6 is more preferably O, S, orNCH₂CH₃.

In another embodiment of this invention R6 is even more preferably O.

In another embodiment of this invention R7 is furyl. In anotherembodiment of this invention R7 is substituted furyl wherein thesubstituted furyl has one or more substituents selected from C(═O)C₁-C₆alkyl, (C₁-C₆ alkyl)-S(O)_(n)—(C₁-C₆ alkyl), and tetrahydrofuran.

In another embodiment of this invention R7 is oxazolyl. In anotherembodiment of this invention R7 is substituted oxazolyl wherein thesubstituted oxazolyl has one or more C₁-C₆ alkyls.

In another embodiment of this invention R7 is piperidinyl. In anotherembodiment of this invention R7 is substituted piperidinyl wherein saidsubstituted piperidinyl has one or more substituents selected from C₁-C₆alkyl, C(═O)OC₁-C₆ alkyl, C(═S)NH(C₃-C₁₀ cycloalkyl), C(═O)C₁-C₆haloalkyl, C(O)OC₁-C₆ alkylOC₁-C₆ alkyl, S(O)_(n)(C₁-C₆ alkyl) andC(═O)C₁-C₆ alkyl.

In another embodiment of this invention R7 is pyrazolyl. In anotherembodiment of this invention R7 is substituted pyrazolyl wherein saidsubstituted pyrazolyl has one or more substituents selected from C₁-C₆alkyl, C₆-C₂₀ aryl, C₁-C₆ haloalkyl, and S(O)_(n)N(C₁-C₆ alkyl)₂.

In another embodiment of this invention R7 is pyridazinyl. In anotherembodiment of this invention R7 is substituted pyridazinyl wherein saidsubstituted pyridazinyl has one or more substituents selected from (═O)and C₁-C₆ alkyl.

In another embodiment of this invention R7 is pyridyl. In anotherembodiment of this invention R7 is substituted pyridyl wherein saidsubstituted pyridyl has one or more C₁-C₆ alkyls.

In another embodiment of this invention R7 is pyrrolidinyl. In anotherembodiment of this invention R7 is substituted pyrrolidinyl wherein saidsubstituted pyrrolidinyl has one or more C(═O)OC(CH₃)₃.

In another embodiment of this invention R7 is thiazolyl. In anotherembodiment of this invention R7 is substituted thiazolyl wherein saidsubstituted thiazolyl has one or more substituents selected from C₁-C₆alkyl and C₁-C₆ haloalkyl.

In another embodiment of this invention R7 is thienyl. In anotherembodiment of this invention R7 is preferably tetrahydrothienyl,thienylC(═O)(C₁-C₆ alkyl), or tetrahydrothienyl-1-oxide. In anotherembodiment of this invention R7 is more preferably thienylC(═O)CH₃.

In another embodiment of this invention, R7 isC₁-C₆alkylOC(═O)C₁-C₆alkyl, OC₁-C₆alkylC₁-C₂₀heterocyclyl,C₁-C₆alkylC₁-C₂₀heterocyclyl, C₁-C₆alkylS(═N—CN)(C₁-C₆alkyl),C₁-C₆alkylS(O)(═N—CN)(C₁-C₆alkyl), C₁-C₆alkylS(O)_(n)(C₁-C₆alkyl-C₁-C₂₀heterocyclyl),C₁-C₆alkylS(O)(═N—CN)(C₁-C₆alkylC₁-C₂₀heterocyclyl),C₁-C₆alkylNH(C(═O)OC₁-C₆alkyl), C₁-C₆alkylC(═O)OC₁-C₆alkyl,C₁-C₆alkyl(C₆-C₂₀aryl)NH(C(═O)OC₁-C₆alkyl),C₁-C₆alkyl(SC₁-C₆alkyl)NH(C(═O)OC₁-C₆alkyl),C₁-C₆alkyl(SC₁-C₆alkylC₆-C₂₀ aryl)NH(C(═O)OC₁-C₆alkyl),C₁-C₆alkyl(NHC(═O)OC₁-C₆alkyl-C₆-C₂₀ aryl)NH(C(═O)OC₁-C₆alkyl),C₁-C₆alkyl(O—C₁-C₆alkylC₆-C₂₀ aryl)NH(C(═O)OC₁-C₆alkyl),C₁-C₆alkylN(C₁-C₆ alkyl)(C(═O)OC₁-C₆alkyl), C₁-C₆alkylNH(C₁-C₆ alkyl),C₆-C₂₀ arylSC₁-C₆haloalkyl,C₁-C₆alkylN(C₁-C₆alkyl)(C(═O)C₁-C₆alkylC₆-C₂₀aryl),C₁-C₆alkylN(C₁-C₆alkyl)(C₁-C₆alkyl),C₁-C₆alkylN(C₁-C₆alkyl)(S(O)_(n)C₁-C₆alkyl), C₁-C₆alkylN(C₁-C₆alkyl)(S(O)_(n)C₁-C₆alkenylC₆-C₂₀aryl),C₁-C₆alkylN(C₁-C₆alkyl)(C(═O)C₁-C₂₀hetertoaryl), C₁-C₆alkylN(C₁-C₆alkyl)(C(═O)OC₁-C₆alkylC₆-C₂₀aryl), NH(C₁-C₆alkylS(O)_(n)C₁-C₆alkyl),NH(C₁-C₆alkylS(O)_(n)C₆-C₂₀aryl), orC₁-C₆alkyl(S(O)_(n)C₁-C₆alkyl)(C(═O)C₁-C₆ alkylS(O)_(n)(C₁-C₆ alkyl).

In another embodiment of this invention, R7 is more preferablyCH(CH₃)CH₂S(═N—CN)CH₃, CH(CH₃)CH₂S(O)(═N—CN)CH₃,CH(CH₃)CH₂SCH₂(chloropyridyl), CH(CH₃)CH₂S(O)(═N—CN)CH₂(chloropyridyl),CH(CH₃)NHC(═O)OC(CH₃)₃, CH₂CH₂C(═O)OCH₃, CH₂NHC(═O)OC(CH₃)₃,CH(CH₂-phenyl)NHC(═O)OC(CH₃)₃, CH(CH₂CH₂SCH₃)NHC(═O)OC(CH₃)₃,CH(CH₃)NHC(═O)OC(CH₃)₃, CH(CH₂CH₂CH₃)NHC(═O)OC(CH₃)₃,CH(CH₂SCH₂-phenyl)NHC(═O)OC(CH₃)₃,CH(CH₂CH₂CH₂CH₂NHC(═O)OCH₂-phenyl)NHC(═O)OC(CH₃)₃,CH(CH(CH₃)OCH₂-phenyl)NHC(═O)OC(CH₃)₃, CH₂(CH₃)N(CH₃)C(═O)OC(CH₃)₃,CH₂(CH₃)NH(CH₃), phenyl-S—CHF₂, CH₂N(CH₃)C(═O)CH(CH₃)pyrazolyl,CH₂N(CH₃)(S(O)₂CH₃), CH₂N(CH₃)(CH₃), CH₂N(CH₃)(S(O)₂CH═CH-phenyl),CH₂N(CH₃)(C(═O)thienyl), CH(CH₃)N(CH₃)(C(O)OCH₂-phenyl), NHCH₂CH₂SCH₃,NHCH₂CH₂S(chlorophenyl), CH₂-thienyl, orCH(CH₃)CH₂(3,5-dimethyltriazolyl).

In another embodiment of this invention R7 is preferably C₁-C₆ alkyl,C₁-C₆ haloalkyl, C₁-C₆ alkenyl, O(C₁-C₆ alkyl), (C₁-C₆alkyl)S(O)_(n)(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(O)_(n)(C₁-C₆ alkyl(C₆-C₂₀aryl)), (C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), 0(C₁-C₆ alkyl)S(O)_(n)(C₁-C₆alkyl), NH(C₁-C₆ alkyl)S(O)_(n)(C₁-C₆ alkyl), N(C₁-C₆ alkyl)(C₁-C₆alkyl-S(O)_(n)C₁-C₆ alkyl, (C₁-C₆ alkyl)S(O)_(n)(C₁-C₆ alkenyl), O(C₁-C₆haloalkyl), N(unsubstituted C₁-C₆ alkyl)(unsubstituted C₁-C₆ alkyl),C₁-C₆ alkylS(O)_(n)(C₁-C₆ alkenyl), O(C₃-C₁₀ cycloalkyl), O(C₁-C₆alkyl)O(C₁-C₆ alkyl), C₁-C₆ alkyl-(C₆-C₂₀ aryl), (unsubstituted C₁-C₆alkyl)S(O)_(n)(unsubstituted C₆-C₂₀ aryl), NH(aryl), C₃-C₁₀ cycloalkyl,NH(C₁-C₆ alkyl), or (C₆-C₂₀ aryl)S(O)_(n)(C₁-C₆ alkyl).

In another embodiment of this invention R7 is more preferably CH₃, CF₃,OC(CH₃)₃, CH(CH₃)CH₂SCH₃, C(CH₃)₂CH₂SCH₃, CH₂CH₂SCH₃, CH(CH₃)₂, C(CH₃)₃,CH₂CF₃, CH₂CH₂C(═O)OCH₃, OCH₂CH₂SCH₃, OCH₂CH₃, CH₂CH₂S(O)CH₃,CH(CH₃)CH₂S(O)CH₃, C(CH₃)₂CH₂S(O)CH₃, NHCH₂CH₂S(O)CH₃,N(CH₃)(CH₂CH₂S(O)CH₃), OCH₂CH₂S(O)CH₃, C(CH₃)₂CH₂S(O)CH₃,CH(CH₃)CH₂S(O)CH₃, CH₂CH₂S(O)CH₃, CH₂CH₂S(O)₂CH₃, C(CH₃)₂CH₂S(O)₂CH₃,CH(CH₃)CH₂S(O)₂CH₃, NHCH(CH₃)CH₂CH₃, NHCH₂CH₂SCH₃, N(CH₃)CH₂CH₂SCH₃,CH(CH₃)CH₂SCH₂CH═CH₂, CH(CH₃)CH₂SCH₂-phenyl, OC(CH₃)₂CF₃,OC(CH₃)₂CH₂CH₂CH₃, O(methylcyclohexyl), OC(CH₃)₂CH₂OCH₃, OCH₂-phenyl,OCH₃, CH═CH₂, CH₂CH₂CH₂Cl, CH₂C(CH₃)₂SCH₃, CH(CH₃)CH(CH₃)SCH₃,cyclopropyl-SCH₃, CH₂CH(CH₃)SCH₃, CH(CH₃)CH₂S(O)_(n)CH₂CH═CH₂,CH(CH₃)C(═O)OCH₂CH₃, CH₂CH(CH₃)S(O)CH₃, OC(CH₃)₂CH₂OCH₃,CH₂CH₂SCH₂-phenyl, CH₂CH₂SCH₂-phenyl, CH₂CH₂SCH₂CH₃, CH₂CH₂SCH(CH₃)₂,CH(CH₃)SCH₃, O-cyclohexyl, OCH(CH₃)CH₂CH₂CH₃, OCH(CH₃)CF₃, OCH₂CH₂OCH₃,NHCH(CH₃)₂, NHCH₂CH₂CH₃, CH₂CH₂cyclopropyl, CH₂cyclopropyl,CH₂CH₂CH═CHCH₃, CH₂CH₂CH═CHCH₃, C₄F₉, NHCH₂CH₃, SCH₂CH₂CH₂CH₃,OCH(CH₃)CH₂CH₂CH₃, OCH₂CH₂CH₂CH₃, CH₂CF₃, NHcyclopropyl, CH═CH₂CH₃,CH(CH₃)(chlorophenyl), C(CH₃)CH₂S(O)CH₃, C(CH₃)CH₂SCH₃, CH(═CH₂)CH₂CH₃,CH₂CH₂C(═O)OCH₃, CH₂SCH₂CH₃, CH₂SCH₃, CH₂CH₂CH₂SCH₃, OCH₂CF₃,NH-(chlorophenyl), phenyl-S(O)—CH₃, CH₂C(CH₃)₂(SCH₃), CH(CH₃)CHOCH₃,CH₂CH(CH₃)SCH₃, CH₂CH(CH₃)₂SCH₃, CH₂CH₂CH₂CH₃, CH(CH₃)CH₂CH₃,1-methyl-2,2-dichlorocyclopropyl, CH(CH₂CH₃)CH₂SCH₃,CH(CH₂CH₃)CH₂S(O)CH₃, or CH(CH₃)CH(CH₃)S(O)CH₃.

In another embodiment of this invention R7 is even more preferablyCH(CH₃)CH₂SCH₃, C(CH₃)₂CH₂SCH₃, CH₂CH₂SCH₃, CH(CH₃)₂, C(CH₃)₃,CH₂CH₂S(O)CH₃, C(CH₃)₂CH₂S(O)CH₃, CH(CH₃)CH₂S(O)CH₃, CH₂CH₂S(O)₂CH₃,C(CH₃)₂CH₂S(O)₂CH₃, CH(CH₃)CH₂S(O)₂CH₃, CH(CH₃)CH₂SCH₂CH═CH₂,CH₂C(CH₃)₂SCH₃, CH(CH₃)CH(CH₃)SCH₃, CH₂CH(CH₃)SCH₃,CH(CH₃)CH₂S(O)_(n)CH₂CH═CH₂, CH₂CH(CH₃)S(O)CH₃, CH₂CH₂SCH₂CH₃,CH₂CH₂SCH(CH₃)₂, CH(CH₃)SCH₃, CH₂SCH₂CH₃, CH₂SCH₃, CH₂CH₂CH₂SCH₃,CH₂CH(CH₃)SCH₃, CH₂CH(CH₃)₂SCH₃, CH(CH₂CH₃)CH₂SCH₃,CH(CH₂CH₃)CH₂S(O)CH₃, or CH(CH₃)CH(CH₃)S(O)CH₃.

In another embodiment of this invention R8 is H, F, Cl, Br, CN, C₁-C₆alkyl, C₁-C₆ alkoxy, C(═O)O(C₁-C₆ alkyl), or S(O)_(n)(C₁-C₆ alkyl). Inanother embodiment of this invention R8 is preferably H, F, Cl, Br, CN,CH₃, OCH₃, S(O)₂CH₃, or C(═O)OCH₂CH₃.

In another embodiment of this invention R8 is even more preferably H orF.

In another embodiment of this invention:

(a) X is CR8;

(b) R1 is H;

(c) R2 is H;

(d) R3 is H;

(e) R4 is C₁ or CH₃;

(f) R5 is H or unsubstituted C₁-C₆ alkyl;

(g) R6 is O;

(h) R7 is (unsubstituted C₁-C₆ alkyl)S(O)_(n)(unsubstituted C₁-C₆alkyl), (unsubstituted C₁-C₆ alkyl)S(O)_(n)(unsubstituted C₁-C₆alkenyl), O(unsubstituted C₁-C₆ alkyl), (C₁-C₆ alkyl);

(i) R8 is H or F; and

(k) n is 0, 1, or 2.

In another embodiment of this invention:

(a) X is CR8;

(b) R1 is H;

(c) R2 is H;

(d) R3 is H;

(e) R4 is Cl;

(f) R5 is unsubstituted C₁-C₆ alkyl;

(g) R6 is O;

(h) R7 is (unsubstituted C₁-C₆ alkyl)S(O)_(n)(unsubstituted C₁-C₆alkyl);

(i) R8 is H or F; and

(k) n is 0, 1, or 2.

While the embodiments have been expressed, other embodiments andcombinations of these expressed embodiments and other embodiments arepossible.

The following scheme illustrates approaches to generatingaminothiazoles. In step a of Scheme I, treatment of a carboxylic acid ofFormula IIa, such as nicotinic acid wherein R1, R2, R3 and X are aspreviously defined, with oxalyl chloride in the presence of a catalyticamount of N,N-dimethylformamide (DMF) in a polar aprotic solvent such as1,2-dichloroethane (DCE) provides the corresponding acid chloride ofFormula IIb. In step b of Scheme I, a commercially available carboxylicacid of Formula IIa, such as nicotinic acid, can be treated with anamino acid ester of Formula III (R4=H) such as glycine methyl esterhydrochloride, in the presence of p-toluenesulfonyl chloride, acatalytic amount of benzyltriethylammonium chloride and an inorganicbase, such as potassium carbonate, in a solvent such as chloroform toafford the amide ester of Formula IVa. Alternatively, the amide esterIVa can be accessed as in step c of Scheme I, where an acid chloride ofFormula IIb is allowed to react with an amino acid ester of Formula III(R4=H, CH₃, phenyl, or isopropyl) such as glycine or (±)-alanine methylester hydrochloride, in the presence of a tertiary amine base such astriethylamine and in a polar aprotic solvent such as DCE oracetonitrile. In step d of Scheme I and in the event wherein R3 is ahalogen and R1, R2, R4 and X are as previously defined, the halogen canbe removed reductively using hydrogen in the presence of a catalyst,such as palladium hydroxide on carbon, in a polar protic solvent such asmethanol to give compounds of Formula IVb, where R3 is H. In step e ofScheme I, reaction of the amide esters of Formula IVa and IVb, whereinR1, R2, R3, R4 and X are as previously defined, with an amine such asmethylamine in a polar protic solvent like ethyl alcohol affords thediamides of Formula V, which upon treatment with phosphorus pentasulfide(step g) or Lawesson's reagent (step h) may yield aminothiazoles ofFormula VIIa. In the event wherein X is CR8 and R4 is H, the diamide ofFormula V, which upon treatment with Lawesson's reagent, may provide thebis-thioamide of Formula VI as in step i of Scheme I. Cyclization toyield the aminothiazole of Formula VIIb is accomplished in two steps, byreaction of the bis-thioamide of Formula VI with trifluoroaceticanhydride as in step j, followed by hydrolysis with sodium hydroxide ina polar protic solvent such as methyl alcohol, as in step k of Scheme I.Alternatively, cyclization to yield the aminothiazole of Formula VIIc,where R4=Cl is accomplished in three steps, by reaction of thebis-thioamide of Formula VI with trifluoroacetic anhydride as in step j,followed by chlorination with a chlorinating agent such asN-chlorosuccinimide in a polar aprotic solvent such as acetonitrile asin step l, and hydrolysis with potassium carbonate in a polar proticsolvent such as methyl alcohol, as in step m of Scheme I.

Another approach to substituted aminothiazoles is illustrated in SchemeII. In step a, the thiazole ester of Formula Xa is formed in one step byreaction of a commercially available thioamide of Formula VIIIa, whereinR1, R2, R3 and X are as previously defined, with a β-ketoester ofFormula IXa such as 2-chloro-4,4,4-trifluoro-3-oxobutyric acid ethylester, wherein R4 is as previously defined, under microwave irradiationconditions in the presence of a base, such as triethylamine, and in asolvent such as ethyl alcohol. Saponification of the ester can beaccomplished as in step b of Scheme II using a base such as sodiumhydroxide in a solvent such as aqueous methyl alcohol to give the acidof Formula XIa. In step c of Scheme II, the tert-butyl carbamate (shown)or other carbamate of Formula XIIa is formed by reaction of the acid ofFormula XIa with diphenyl phosphoryl azide (DPPA) and the appropriatealcohol with heating. Alkylation of the carbamate nitrogen with an alkylhalide such as iodomethane, in the presence of a base such as sodiumhydride and in a polar aprotic solvent such as N,N-dimethylformamide(DMF) may yield the compounds of Formula XIIIa as shown in step d ofScheme II. Finally in step e of Scheme II, deprotection of the amine inthe presence of an acid, such as trifluoroacetic acid (TFA), may affordthe aminothiazole of Formula VIId.

Yet another approach to aminothiazoles is through coupling of thedesired amine-protected thiazole and the heterocycle as in Scheme III.In step a, a 2-halo-4-substituted thiazole-5-carboxylic acid ethyl esterof Formula XIVa, wherein R4 is as previously defined, is hydrolyzedunder basic conditions, such as with lithium hydroxide hydrate, in asolvent system such as aqueous tetrahydrofuran (THF) to afford thecorresponding acid of Formula XVa. Compounds of Formula XVa aretransformed to the acyl azide of Formula XVIa by reaction with diphenylphosphoryl azide as in step b of Scheme III. In step c of Scheme III, aCurtius rearrangement, followed by the trapping of the resultingisocyanate with tert-butyl alcohol, affords the tert-butyloxycarbonyl(Boc) protected 5-amino thiazole of Formula XVIIa, wherein R4 is aspreviously defined. Alkylation of the carbamate functionality with analkyl halide such as iodomethane, in the presence of a base such assodium hydride and in a polar aprotic solvent such as DMF yields thealkyl carbamate of Formula XVIIIa, as shown as step d in Scheme III. Instep e of Scheme III, compounds of Formula XVIIa or XVIIIa, wherein R4and R5 are as previously defined, can be allowed to react under Suzukicoupling conditions with a boronic acid of Formula XIXa, wherein X, R1,R2 and R3 are as previously defined, to provide the heterocycle-coupledthiazole of Formula XIIIb. In the event that R5 is not H, the Boc-groupcan be removed under acidic conditions such as trifluoroacetic acid(TFA) in a polar aprotic solvent like dichloromethane to give compoundsof Formula VIIe as in step f of Scheme III. When R5 is H, the Boc-groupcan be removed under acidic conditions such as methanolic hydrochloricacid to yield compounds of Formula VIIf as in step g of Scheme III. Instep h, when R4 is H, compounds of Formula XVIIIb can be converted tocompounds of Formula XVIIIa, wherein R4 is specifically a halogen. Thiscan be accomplished by treatment of XVIIIb with a halogenating reagentsuch as N-chlorosuccinimide or N-bromosuccinimide, in a polar aproticsolvent such as acetonitrile to afford 4-halo-thiazole of FormulaXVIIIa.

In step a of Scheme IV, the compounds of Formula XVIIIc, wherein R4 isas previously defined and R5 is H, can be treated with an acid chlorideof Formula XXa, wherein R6 is O and R7 is as previously defined, in thepresence of a base such as triethylamine in a polar aprotic solvent suchas dichloroethane (DCE) to yield compounds of Formula XXI. In step b ofScheme IV the Boc group can be removed under acidic conditions, such astrifluoroacetic acid in a polar aprotic solvent such a dichloromethane(DCM) to provide compounds of Formula XXII. The acid chlorides used inthe acylation reactions herein are either commercially available or canbe synthesized by those skilled in the art. In step c of Scheme IV, thecompounds of Formula XXII can undergo alkylation with an alkyl halidesuch as iodomethane, in the presence of a base such as sodium hydride orpotassium carbonate and in a polar aprotic solvent such asN,N-dimethylformamide (DMF) to yield the alkylated compounds of FormulaXXIII. In step d of Scheme IV, compounds of Formula XXII or XXIII,wherein R4, R5, R6 and R7 are as previously defined, can be allowed toreact under Suzuki coupling conditions with a boronic acid of FormulaXIXb, wherein X, R1, R2 and R3 are as previously defined, to provide theheterocycle-coupled thiazole of Formula Ia.

In step a of Scheme V, compounds of Formula VIIa-k, wherein X, R1, R2,R3, R4 and R5 are as previously defined, can be treated with an acidchloride of Formula XXb, wherein R6 is O and R7 is as previouslydefined, in the presence of a base such as triethylamine in a polaraprotic solvent such as dichloroethane (DCE) to yield compounds ofFormula Ib.

In step a of Scheme VI, ureas and carbamates are made from theaminothiazoles of Formula VIIa-k. Compounds of Formula VIIa-k, whereinX, R1, R2, R3, R4 and R5 are as previously defined, are allowed to reactwith phosgene to provide the intermediate carbamoyl chloride. In steps band c of Scheme VI, the carbamoyl chloride is treated with an amine oralcohol, respectively, to generate an urea of Formula Ic or a carbamateof Formula Id, respectively. Alkylation of the urea nitrogen ofcompounds of Formula Ic with an alkyl halide such as iodomethane, in thepresence of a base such as sodium hydride and in a polar aprotic solventsuch as N,N-dimethylformamide (DMF) yields compounds of Formula Ie asshown in step d of Scheme VI.

Oxidation of the sulfide to the sulfoxide or sulfone is accomplished asin Scheme VII where (˜) can be any number of atoms and bonds previouslymentioned within the scope of this invention. The sulfide of Formula If,wherein X, R1, R2, R3, R4 and R5 are as previously defined, is treatedwith an oxidant such as sodium perborate tetrahydrate in a polar proticsolvent such as glacial acetic acid to give the sulfoxide of Formula Igas in step a of Scheme VII. The sulfoxide of Formula Ig can be furtheroxidized to the sulfone of Formula Ih by sodium perborate tetrahydratein a polar protic solvent such as glacial acetic acid as in step b ofScheme VII. Alternatively, the sulfone of Formula Ih can be generated ina one-step procedure from the sulfide of Formula If by using theaforementioned conditions with ≧2 equivalents of sodium perboratetetrahydrate, as in step c of Scheme VII.

In step a of Scheme VIII, compounds of Formula XIIb, wherein X, R1, R2,R3 and R4 are as previously defined, can be treated with an acidchloride of Formula XXc, wherein R6 is O and R7 are as previouslydefined, in the presence of a base such as triethylamine in a polaraprotic solvent such as dichloroethane (DCE) to yield compounds ofFormula XXIV. In step b of Scheme VIII the Boc group of XXIV can beremoved under acidic conditions, such as trifluoroacetic acid (TFA) in apolar aprotic solvent such a dichloromethane to provide compounds ofFormula Ii. Alkylation of the amide functionality with an alkyl halidesuch as benzoic acid chloromethyl ester, in the presence of a base suchas sodium hydride and in a polar aprotic solvent such asN,N-dimethylformamide (DMF) yields alkyl amide of Formula Ij, as shownin step c of Scheme VIII.

In step a of Scheme IX, compounds of Formula XIIIc, wherein X, R1, R2,R3 and R5 are as previously defined, can be treated with anelectrophilic source of halogen, such as N-bromosuccinimide orN-iodosuccinimide in a polar aprotic solvent such as acetonitrile toyield compounds of Formula XIIId, wherein R4 is limited to halogens.Palladium-catalyzed cross coupling reactions such as the Stille couplingon compounds of Formula XIIId can be performed as in step b using apalladium catalyst such as bis(triphenylphosphine)palladium(II) chloridein a polar aprotic solvent such as dioxane to yield carbamates ofFormula XXV. Also, compounds of the formula XIIIe, where R4 is a cyanogroup, can be prepared by treating the compound of the formula XIIIdwith CuCN in a solvent such as N,N-dimethylformamide (DMF) at a suitabletemperature as in step c.

In step a of Scheme X, the compound of Formula XVIIb where R4 is H canbe treated with BOC-anhydride in the presence of a base such astriethylamine in a polar aprotic solvent such as tetrahydrofuran (THF)to yield compounds of Formula XXV. Next, as in step b, compounds ofFormula XXV can be allowed to react under Suzuki coupling conditionswith a boronic acid of Formula XIXc, wherein X, R1, R2, R3 and R4 are aspreviously defined, to provide the heterocycle-coupled thiazole ofFormula XXVI. In step c, compounds of Formula XXVI can be treated withan electrophilic source of halogen, such as Selectfluor™, in a mixtureof polar aprotic solvents such as acetonitrile and N,N-dimethylformamide(DMF) to yield compounds of Formula XXVII, wherein R4 is limited tohalogens. Finally, one of the BOC-groups can be removed under acidicconditions such as trifluoroacetic acid (TFA) in a polar aprotic solventsuch as dichloromethane (DCM) to yield compounds of Formula XIIc as instep d of Scheme X, where R1, R2, R3 and R4 are as previously defined.

Oxidation of the sulfide to the sulfoximine is accomplished as in SchemeXI. The sulfide of Formula Ik, wherein X, R1, R2, R3, R4 and R5 are aspreviously defined, is oxidized as in step a with iodobenzene diacetatein the presence of cyanamide in a polar aprotic solvent such asmethylene chloride (DCM) to give sulfilimine of the Formula Im. Thesulfilimine of Formula Im may be further oxidized to the sulfoximine ofFormula In with mCPBA in the presence of a base such as potassiumcarbonate in a protic polar solvent system such as ethanol and water asin step b of Scheme XI.

In step a of Scheme XII, the compound of Formula VIIIb, wherein X, R1,R2 and R3 are as previously defined, can be treated with ethylbromopyruvate in a polar protic solvent such as ethanol to yieldcompounds of Formula)(XVIII. In step b of Scheme XII, the5-bromothiazole of Formula XXIX is formed by reaction of the thiazoleester of Formula XXVIII with a base such as postassiumbis(trimethylsilyl)amide and N-bromosuccinimide in a polar aproticsolvent such as THF. In step c, the bromine is displaced with sodiumazide in a solvent system such as N,N-dimethylformamide (DMF)/H₂O. Theresultant azide was thermally reduced (75° C.) to give the5-aminothiazole of Formula XXX in Scheme XII.

In step a of Scheme XIII, the thioamide Iq is prepared from the amide ofFormula Ip. The compound of Formula Ip, wherein X, R1, R2, R3, R4, R5and R7 are as previously defined, is allowed to react under microwaveirradiation conditions with Lawesson's reagent in a solvent such asdioxane to give the thioamide of Formula Iq in Scheme XIII.

In step a of Scheme XIV, compounds of Formula VIIg, wherein X, R1, R2,R3, R4, and R5 are as previously defined, can be treated withsubstituted isothiocyanates of Formula XXXI where R9 is as previouslydefined, in refluxing dioxane to yield compounds of Formula Ir. In stepb of Scheme XIV, the S-alkylated pseudothioureas of Formula Is can beformed by treating thioureas of Formula Ir with alkylating agents inrefluxing ethanol under basic conditions, wherein each R9 can be thesame or different.

In step a of Scheme XV, the compound of Formula XXXV wherein R4 is asdefined previously, can be allowed to react under Suzuki couplingconditions with a boronic acid of Formula XIXd, wherein R1, R2, R3 and Xare as defined previously to provide the heterocycle-coupled thiazole ofFormula XXII. In step b of Scheme XV, compounds of the Formula XXXII,wherein R1, R2, R3, R4 and X are as defined previously, can be convertedto compounds of the Formula XXXIIIa, wherein R1, R2, R3, R4 and X are asdefined previously by treatment with a nitrating reagent such as amixture of fuming nitric acid and concentrated sulfuric acid at asuitable temperature. In step c, compounds of Formula XXXIIIa, whereinR1, R2, R3, and X are as defined previously and R4 is a leaving groupsuch as chloro, can be treated with a nucleophile such as sodiumthiomethoxide to produce the compounds of Formula XXXIIIb, wherein R1,R2, R3, and X are as defined previously and R4 is thioalkyl. In step d,compounds of Formula XXXIIIb can be converted to compounds of FormulaVIIh, wherein R1, R2, R3, R4 and X are as defined previously and R5 isH, by treatment with molecular hydrogen in the presence of a catalystsuch as Pd on C and an acid such as acetic acid in a solvent such asethyl acetate.

In step a of Scheme XVI, compounds of Formula VIIi, wherein X, R1, R2,R3, R4 and R5 are as previously defined, can be treated with an acid ofFormula XXXIV, wherein R6 is O and R7 is as previously defined, in thepresence of a coupling reagent such as1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCHCl) anda base such as N,N-dimethylaminopyridine (DMAP) in a polar aproticsolvent such as dichloroethane (DCE) to yield compounds of Formula It.

Another approach to substituted aminothiazoles is illustrated in SchemeXVII. In step a, the thiazole ester of Formula Xb is formed in one stepby reaction of a commercially available thioamide of Formula VIIIb,wherein R1, R2, R3 and X are as previously defined, with a β-ketoesterof Formula IXb such as ethyl 2-chloro-3-oxobutanoate, wherein R4 is aspreviously defined, and heating to 70-80° C. in a solvent such as ethylalcohol. Saponification of the ester can be accomplished as in step b ofScheme XVII using a base such as lithium hydroxide in a solvent such astetrahydrofuran (THF) to give the acid of Formula XIb. In step c ofScheme XVII, the tert-butyl carbamate of Formula XIIc is formed byreaction of the acid of Formula XIb with a chlorinating agent such asthionyl chloride to give the acid chloride, treatment of the acidchloride with sodium azide in a biphasic solution such as dichloroethane(DCE) and water to give the acyl azide, and then heating the acyl azidein tert-butanol as solvent. Alkylation of the carbamate nitrogen with analkyl halide such as iodomethane, in the presence of a base such assodium hydride and in a polar aprotic solvent such asN,N-dimethylformamide (DMF) may yield the compounds of Formula XIIIf asshown in step d of Scheme XVII. Finally in step e of Scheme XVII,deprotection of the amine in the presence of an acid, such as 4M HCl indioxane, affords the aminothiazole as the HCl salt as in Formula VIIj.

Another approach to aminothiazoles is through coupling of the desiredamine-protected thiazole and the heterocycle as in Scheme XVIII. In stepa, a 2-halo-4-substituted thiazole-5-carboxylic acid ethyl ester ofFormula XIVb, wherein R4 is as previously defined, is hydrolyzed underbasic conditions, such as lithium hydroxide hydrate, in a solvent systemsuch as aqueous tetrahydrofuran (THF) to afford the corresponding acidof Formula XVb. Compounds of Formula XVb are transformed to thetert-butyl carbamate of Formula XVIIc by reaction with diphenylphosphoryl azide in tert-butanol as solvent in the presence of a basesuch as triethylamine as in step b of Scheme XVIII. Alkylation of thecarbamate functionality with an alkyl halide such as iodomethane, in thepresence of a base such as sodium hydride and in a polar aprotic solventsuch as N,N-dimethylformamide (DMF) yields the alkyl carbamate ofFormula XVIIId, as shown in step c of Scheme XVIII. In step d of SchemeXVIII, compounds of Formula XVIIc or XVIIId, wherein R4 and R5 are aspreviously defined, can be allowed to react under Suzuki couplingconditions with a boronic acid of Formula XIXe, wherein X, R1, R2 and R3are as previously defined, to provide the heterocycle-coupled thiazoleof Formula XIIIg. In the event that R5 is as previously defined, theBoc-group can be removed under acidic conditions such as 4M HCl indioxane to give compounds of Formula VIIk as in step e of Scheme XVIII.

In step a of Scheme XIX, compounds of Formula VIIa-k, wherein X, R1, R2,R3, R4 and R5 are as previously defined, can be treated with an acidchloride of Formula XXd, wherein R6 is O and R7 is as previouslydefined, in the presence of a catalyst such as N,N-dimethylaminopyridine(DMAP) and a base such as pyridine in a polar aprotic solvent such asdichloromethane (DCM) to yield compounds of Formula Iv.

In step a of Scheme XX, compounds of Formula XXXVI can be treated withan electrophilic source of halogen such as N-chlorosuccinimide in apolar aprotic solvent such as acetonitrile to yield compounds of FormulaXXXVII. The Boc-group in compounds of Formula XXXVII can be removedunder acidic conditions such as trifluoroacetic acid (TFA) in a polaraprotic solvent such as dichloromethane as in step b to give compoundsof Formula XXXVIII. In step c compounds of Formula XXXVIII can betreated with 3-methylsulfanyl-propionyl chloride in the presence of abase such as N,N-dimethyl amino-pyridine in a polar aprotic solvent suchas dichloroethane (DCE) to yield compounds of Formula XXXIX. In step dcompounds of Formula XXXVIII can be treated with2-methyl-3-methylsulfanyl-propionyl chloride in the presence of a basesuch as N,N-dimethylamino-pyridine in a polar aprotic solvent such asdichloroethane (DCE) to yield compounds of Formula XXXX.

In step a of Scheme XXI, compounds of Formula XXXI can be treated withan electrophilic source of halogen such as N-chlorosuccinimide in apolar aprotic solvent such as acetonitrile to yield compounds of FormulaXXXXII. The Boc-group in compounds of Formula XXXXII can be removedunder acidic conditions such as trifluoroacetic acid (TFA) in a polaraprotic solvent such as dichloromethane (DCM) as in step b to givecompounds of Formula XXXXIII. In step c compounds of Formula XXXXIII canbe treated with 3-methylsulfanyl-propionyl chloride in the presence of abase such as N,N-dimethyl amino-pyridine in a polar aprotic solvent suchas dichloroethane (DCE) to yield compounds of Formula XXXXIV. In step dcompounds of Formula XXXXIII can be treated with2-methyl-3-methylsulfanyl-propionyl chloride in the presence of a basesuch as N,N-dimethylamino-pyridine in a polar aprotic solvent such asdichloroethane (DCE) to yield compounds of Formula XXXXV.

EXAMPLES

The examples are for illustration purposes and are not to be construedas limiting the invention disclosed in this document to only theembodiments disclosed in these examples.

Starting materials, reagents and solvents which were obtained fromcommercial sources were used without further purification. Anhydroussolvents were purchased as Sure/Seal™ from Aldrich and were used asreceived. Melting points were obtained on a Thomas Hoover Unimeltcapillary melting point apparatus or an OptiMelt Automated Melting PointSystem from Stanford Research Systems and are uncorrected. Molecules aregiven their known names, named according to naming programs within ISISDraw, ChemDraw or ACD Name Pro. If such programs are unable to name amolecule, the molecule is named using conventional naming rules. All NMRare in ppm (δ) and were recorded at 300, 400 or 600 MHz unless otherwisestated.

Example 1 Preparation of [(pyridine-3-carbonyl)-amino]-acetic acidmethyl ester

Method A

An ice-cold suspension of the hydrochloride salt of nicotinoyl chloride(5 grams (g), 28 millimoles (mmol)) in dichloroethane (DCE, 150milliliters (mL)) was treated with glycine methyl ester hydrochloride(3.7 g, 29 mmol) in portions, followed by dropwise addition oftriethylamine (Et₃N, 15.6 mL, 0.111 moles (mol)) via syringe. Thereaction mixture was allowed to come to room temperature under nitrogenover 14 hours (h), washed with water (2×100 mL), brine (100 mL), driedover magnesium sulfate (MgSO₄) and purified by silica gel chromatography(ethyl acetate/hexanes gradient) to yield an orange solid (1.8 g, 33%).The aqueous washings of the crude reaction mixture were saturated withsodium chloride (NaCl), extracted with dichloromethane (CH₂Cl₂) andpurified by silica gel chromatography (ethyl acetate/hexanes gradient)to yield a yellow solid (1.6 g, 29%; total yield 3.4 g, 62%): mp 66-68°C.; ¹H NMR (300 MHz, CDCl₃) δ 9.04 (d, J=2.2 Hz, 1H), 8.76 (dd, J=4.8,1.5 Hz, 1H), 8.15 (dt, J=8.1, 1.8 Hz, 1H), 7.42 (dd, J=8.1, 4.8 Hz, 1H),6.84 (br s, 1H), 4.28 (d, J=5.2 Hz, 2H), 3.82 (s, 3H); ESIMS m/z 195(M+1).

Method B

A mixture of nicotinic acid (10 g, 81 mmol), p-toluenesulfonyl chloride(17 g, 89 mmol), benzyltriethylammonium chloride (1.85 g, 8.1 mmol), andpotassium carbonate (K₂CO₃, 44.9 g, 320 mmol) in chloroform (CHCl₃, 500mL) was stirred mechanically at 40° C. for 1 h. Glycine methyl esterhydrochloride (10.2 g, 81 mmol) and K₂CO₃ (11.2 g, 80 mmol) were thenadded and stirred at 50° C. for 90 minutes (min). The reaction mixturewas filtered through Celite® and the filtrate was concentrated underreduced pressure. The crude product was purified by silica gel columnchromatography (2% methanol/ethyl acetate) to give the desired productas an orange gum which solidified upon standing at room temperature (4.7g, 30%): ¹H NMR (400 MHz, CDCl₃) δ 9.04 (d, J=2.2 Hz, 1H), 8.76 (dd,J=4.8, 1.5 Hz, 1H), 8.15 (dt, J=8.1, 1.8 Hz, 1H), 7.42 (dd, J=8.1, 4.8Hz, 1H), 6.84 (br s, 1H), 4.28 (d, J=5.2 Hz, 2H), 3.87 (s, 3H); ESIMSm/z 195 (M+1).

Example 2 Preparation of 2-[(pyridine-3-carbonyl)-amino]-propionic acidmethyl ester

(±)-Alanine methyl ester hydrochloride salt (35.2 g, 280 mmol) and Et₃N(58.5 mL, 420 mmol) were sequentially added to a stirred solution ofnicotinoyl chloride (19.8 g, 140 mmol) in acetonitrile (800 mL) andstirred at ambient temperature for 10 min and then 80° C. for 2 h. Thereaction mixture was poured into a separatory funnel containing brineand ethyl acetate. The biphasic mixture was separated, and the organiclayer was washed one time with brine, dried over MgSO₄, filtered andconcentrated to dryness. The crude product was triturated in 80% ethylacetate/hexanes overnight at ambient temperature. The solids wereremoved by filtration over Celite® and the filtrate was concentrated invacuo to give the desired product as a clear brown oil (20 g, 69%): ¹HNMR (300 MHz, CDCl₃) δ 9.04 (d, J=2.2 Hz, 1H), 8.75 (dd, J=4.9, 1.4 Hz,1H), 8.13 (dt, J=7.7, 1.9 Hz, 1H), 7.40 (dd, J=8.0, 4.9 Hz, 1H), 6.92(br s, 1H), 4.82 (m, 1H), 3.81 (s, 3H), 1.55 (d, J=7.1 Hz, 3H); ESIMSm/z 209 (M+1), m/z 207 (M-1).

Example 3 Preparation of[(2-chloro-5-fluoropyridine-3-carbonyl)-amino]-acetic acid methyl ester

To a solution of 2-chloro-5-fluoro-nicotinic acid (21.9 g, 124 mmol) inDCE (300 mL) were added oxalyl chloride (21.5 mL, 249 mmol) and then adrop of N,N-dimethylformamide (DMF). After the vigorous bubblingsubsided (ca 5 min), the reaction mixture was heated to 65° C. for 1 h.The reaction solvents were removed in vacuo to afford the acid chlorideas a yellow oil which was used directly in the next step. The freshlymade acid chloride was dissolved in 1,4-dioxane (300 mL), and thesolution was cooled to 0° C. in an ice bath. Glycine methyl esterhydrochloride (16.3 g, 130 mmol) and then Et₃N (50 mL, 370 mmol) wereadded. After stirring for 10 min, the solution was allowed to warm toambient temperature and was then heated to reflux for 1.5 h. LC-MSanalysis of a quenched aliquot (water/ethyl acetate) showed incompleteconversion to the desired product so additional glycine methyl esterhydrochloride (15 g, 130 mmol), Et₃N (20 mL, 143 mmol), and 1,4-dioxane(200 mL) were added, and the reaction mixture was heated at refluxovernight. LC-MS analysis of a quenched aliquot (water/ethyl acetate)showed no starting material and 74% of the desired product. The reactionmixture was cooled and then added to a separatory funnel containingwater and ethyl acetate. After separating the layers, the organic layerwas washed with water and brine. To the initial aqueous layer was addedsalt and then ethyl acetate. After separation, the organic layer waswashed with water and brine. The combined organic layers were dried overMgSO₄, filtered, and concentrated in vacuo. The crude material waspurified via silica gel chromatography (40% to 70% ethylacetate/hexanes) to afford a brown oil (20.5 g, 67%): ¹H NMR (300 MHz,CDCl₃) δ 8.36 (d, J=3.0 Hz, 1H), 7.92 (dd, J=7.7, 3.0 Hz, 1H), 7.32 (brs, 1H), 4.27 (d, J=5.2 Hz, 2H), 3.82 (s, 3H); ESIMS m/z 247 (M+1), m/z245 (M-1).

Example 4 Preparation of [(5-fluoropyridine-3-carbonyl)-amino]-aceticacid methyl ester

To a solution of [(2-chloro-5-fluoropyridine-3-carbonyl)-amino]-aceticacid methyl ester (4.65 g, 18.9 mmol) in methanol (200 mL) in a Parrvessel was added Et₃N (3.15 mL, 22.6 mmol) and palladium hydroxide oncarbon (1.5 g, 20 wt % Pd, moisture 60%). The vessel was evacuated andthen put under an atmosphere of hydrogen (initial pressure 42 psi).After 5 min the hydrogen pressure was 14 psi. The catalyst was removedvia suction filtration over Celite® and then the filtrate wasconcentrated. Purification by silica gel chromatography (0 to 100% ethylacetate/hexanes) afforded a light yellow solid (3.83 g, 95%): mp 80-82°C.; ¹H NMR (300 MHz, CDCl₃) δ 8.84 (s, 1H), 8.62 (d, J=2.7 Hz, 1H), 7.87(m, 1H), 7.00 (br s, 1H), 4.27 (d, J=5.3 Hz, 2H), 3.82 (s, 3H); ESIMSm/z 213 (M+1).

Example 5 Preparation of N-Methylcarbamoylmethyl-Nicotinamide

A suspension of [(pyridine-3-carbonyl)-amino]-acetic acid methyl ester(1.5 g, 7.7 mmol) and methylamine (33 wt % in absolute ethanol, 3.86 mL,38.6 mmol) in ethanol (8 mL) was heated at 55° C. in a Parr reactor for6 h. The mixture was cooled and then concentrated under reduced pressureto yield the product as a iridescent beige plates (1.41 g, 94%): ¹H NMR(300 MHz, DMSO-d₆) δ 9.05 (d, J=2.2 Hz, 1H), 9.00 (t, J=5.8 Hz, 1H),8.77 (d, J=4.0 Hz, 1H), 8.23 (br d, J=8.1 Hz, 1H), 7.90 (q, J=4.1 Hz,1H), 7.53 (dd, J=7.7, 4.7 Hz, 1H), 3.86 (d, J=5.8 Hz, 2H), 2.61 (d,J=4.4 Hz, 3H); IR (KBr) 3314, 1641 cm⁻¹; ESIMS m/z 194 (M+1).

Example 6 Preparation of N-(1-methylcarbamoyl-ethyl)nicotinamide

To a solution of 2-[(pyridine-3-carbonyl)-amino]-propionic acid methylester (10.4 g, 50 mmol) in ethanol (50 mL) was added methylamine (24 g,33 wt % solution in ethanol, 250 mmol). The reaction mixture was heatedat 55° C. for 45 min. The solvents were removed in vacuo and the residuewas recrystallized from hot ethyl acetate and hexanes. The yellowcrystals thus obtained were washed with cold ethyl acetate and dried togive the desired product (5.2 g, 50%): ¹H NMR (300 MHz, DMSO-d₆) δ 9.05(br s, 1H), 8.77-8.70 (m, 2H), 8.24 (m, 2H), 7.89 (br s, 1H), 7.50 (m,1H), 2.59 (d, J=4.7 Hz, 3H), 1.33 (d, J=7.4 Hz, 3H); ESIMS m/z 208.1(M+1), m/z 206.1 (M-1).

Example 7 Preparation of 5-fluoro-N-methylcarbamoylmethyl-nicotinamide

To a solution of [(5-fluoropyridine-3-carbonyl)-amino]-acetic acidmethyl ester (2.96 g, 14.0 mmol) in ethanol (15 mL) was addedmethylamine (1.5 g, 33 wt % solution in ethanol, 70 mmol). This clearsolution was then immediately put onto a 55° C. heating mantle for 10min at which time the product had precipitated out of solution. Themixture was filtered in vacuo and the precipitate was washed withethanol. The filtrate was concentrated and recrystallized from hotethanol. This process was repeated again to give a white fluffy material(2.11 g, 72%): mp 201-202° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.10 (m, 1H),8.93 (s, 1H), 8.76 (d, J=2.5 Hz, 1H), 8.10 (m, 1H), 7.95 (br s, 1H),3.86 (d, J=5.8 Hz, 2H), 2.61 (d, J=4.4 Hz, 3H); ESIMS m/z 212 (M+1), m/z210 (M-1).

Example 8 Preparation of methyl-(2-pyridin-3-yl-thiazol-5-yl)-amine

A suspension of phosphorus pentasulfide (1.73 g, 7.8 mmol) andN-methylcarbamoylmethyl-nicotinamide (1 g, 5 mmol) in dry toluene (10mL) was stirred at reflux under nitrogen for 16 h. The mixture wascooled to room temperature and then dry pyridine (4 mL) was added. Themixture was stirred at reflux under nitrogen for 8 h, then it was cooledto room temperature and the organic layer was removed. The dark residuewas treated with hot saturated aqueous sodium bicarbonate (Na₂CO₃, 40mL) and the aqueous layer was extracted with ethyl acetate (2×50 mL).The combined organic extracts were washed with brine (50 mL), dried overmagnesium sulfate (MgSO₄), and purified by silica gel chromatography (1%methanol in dichloromethane) to yield a brown amorphous solid (0.22 g,22%): mp 141-146° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.97 (d, J=2.4 Hz, 1H),8.53 (dd, J=5.0, 1.8 Hz, 1H), 8.06 (ddd, J=7.2, 3.3, 0.6 Hz, 1H), 7.31(ddd, J=5.5, 4.7, 0.5 Hz, 1H), 6.96 (s, 1H), 2.97 (d, J=5.0 Hz, 3H);ESIMS m/z 192 (M+1).

Example 9 Preparation ofmethyl-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-amine

To a 10 mL microwave vessel containing DCE (5 mL) was addedN-(1-methylcarbamoyl-ethyl)nicotinamide (207 mg, 1.0 mmol) followed byLawesson's reagent(2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide,404 mg, 1.0 mmol) in one portion. The heterogeneous mixture was heatedin a microwave for 5 min at 130° C. The reaction mixture was partitionedbetween CH₂Cl₂ and saturated aqueous sodium bicarbonate (NaHCO₃). Thelayers were separated and the organic layer was washed once with brine.The solution was dried over MgSO₄, filtered and concentrated in vacuo.The crude material was purified by silica gel column chromatography(ethyl acetate) to give the desired product as an orange solid (141 mg,68%): mp 84-87° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.98 (d, J=1.7 Hz, 1H),8.51 (dd, J=4.9, 1.7 Hz, 1H), 8.08 (dt, J=8.0, 1.7 Hz, 1H), 7.29 (m,1H), 3.00 (s, 3H), 2.30 (s, 3H); ESIMS m/z 206.4 (M+1), m/z 204.2 (M-1).

Example 10 Preparation of2,2,2-trifluoro-N-[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-N-methyl-acetamide(Compound 1)

To a 10 mL microwave tube was added5-fluoro-N-methylcarbamoylmethyl-nicotinamide (211 mg, 1.00 mmol), 4 Åmolecular sieves (100 mg, spheres), Lawesson's reagent (404 mg, 1.00mmol) and then toluene (5 mL). The tube was capped and heated to 130° C.for 30 seconds via microwave irradiation. The resulting orange solutionwas diluted with CH₂Cl₂ and filtered to remove the sieves. This solutionwas concentrated in vacuo to a semi-solid. To this crude material wasadded CH₂Cl₂ (2 mL) and trifluoroacetic anhydride (2 mL). Gas evolutionwas noted immediately. After stirring for 2 h at room temperature, thesolvents were removed in vacuo. The residue was partitioned betweenCH₂Cl₂ and pH 7.0 buffer. The layers were separated and the buffer wasextracted with CH₂Cl₂. The combined organic extracts were dried overMgSO₄, filtered, and concentrated in vacuo. Purification by silica gelchromatography (0 to 100% ethyl acetate/hexanes) afforded the product asa white solid (282 mg, 92%): mp 168-170° C.; ¹H NMR (300 MHz, CDCl₃)mixture of isomers δ 8.98 and 8.95 (2 br s, 1H), 8.55 and 8.54 (m andapp d, J=2.4 Hz, 1H), (dt, J=9.0 Hz, 2.2 Hz, 1H), 7.80 (s, 1H), 3.75 and3.47 (2 s, 3H); ESIMS m/z 306 (M+1).

The following compounds were made via the methods in the previousexamples.

2,2,2-Trifluoro-N-methyl-N-(2-pyridin-3-yl-thiazol-5-yl)-acetamide(Compound 2)

Purification by silica gel chromatography (0 to 100% ethylacetate/hexanes) afforded the product as an orange solid (1.13 g, 65%):mp 154-158° C.; ESIMS m/z 306.4 (M+1).

N-(4-Ethyl-2-pyridin-3-yl-thiazol-5-yl)-2,2,2-trifluoro-N-methyl-acetamide(Compound 3)

The compound was isolated after purification via silica gelchromatography eluting with an ethyl acetate/hexanes gradient to yieldan amber gum (0.98 g, 63%): IR (thin film) 1717 cm⁻¹; ESIMS m/z 318.21(M+3).

2,2,2-Trifluoro-N-methyl-N-(4-phenyl-2-pyridin-3-yl-thiazol-5-yl)-acetamide(Compound 4)

The compound was isolated after purification via silica gelchromatography eluting with a gradient of ethyl acetate in hexanes toyield an amorphous yellow solid (0.17 g, 31%): IR (thin film) 1674 cm⁻¹;ESIMS m/z 365.4 (M+2).

N-Ethyl-2,2,2-trifluoro-N-(4-phenyl-2-pyridin-3-yl-thiazol-5-yl)-acetamide(Compound 5)

The compound was isolated after purification via silica gelchromatography (ethyl acetate in hexanes) to yield a yellow solid (0.89g, 75%): mp 81-92° C.; IR (KBr) 1713 cm⁻¹; ESIMS m/z 379.4 (M+2).

Example 11N-(4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-2,2,2-trifluoro-N-methyl-acetamide(Compound 6)

A suspension of2,2,2-trifluoro-N-methyl-N-(2-pyridin-3-yl-thiazol-5-yl)-acetamide (1.0g, 3.5 mmol) and N-chlorosuccinimide (0.557 g, 4.2 mmol) in acetonitrile(30 mL) was heated to 63° C. under nitrogen for 3 h. The reactionmixture was cooled to room temperature and it was treated withadditional N-chlorosuccinimide (0.557 g, 4.2 mmol) and heated to 35° C.under nitrogen for 2 h. The reaction mixture was cooled and concentratedunder reduced pressure. The residue was redissolved in dichloromethane(80 mL) and washed with water (70 mL). The aqueous layer wasre-extracted with methylene chloride (100 mL). The combined organiclayers were washed with water (50 mL) and brine (50 mL), dried oversodium sulfate, filtered, concentrated under reduced pressure andpurified using reverse phase chromatography. The product eluted with agradient of acetonitrile in water. The desired product was isolated as athick brown gum (0.337 g, 30%): ¹H NMR (400 MHz, CDCl₃) δ 9.12 (br, 1H),8.75 (br, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.28 (br, 1H), 3.40 (s, 3H); ¹⁹FNMR (376 MHz, CDCl₃) δ −69.3; ESIMS m/z 324.3 (M+2); IR (thin film) 1772cm⁻¹.

Example 12 Synthesis of(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-methyl-amine

A solution ofN-(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-2,2,2-trifluoro-N-methyl-acetamide(0.337 g, 1 mmol) in ice-cold methanol (18 mL) was treated withpotassium carbonate (0.434 g, 3.1 mmol) and stirred under nitrogen for20 min. The solids were removed by filtration, and the filtrate wasconcentrated under reduced pressure and it was adsorbed onto silica gel.Purification by silica gel chromatography eluting with a gradient ofethyl acetate in hexanes afforded a bright yellow solid (0.195 g, 82%):mp 79° C. (dec); ¹H NMR (400 MHz, CDCl₃) δ 8.97 (d, J=2.1 Hz, 1H), 8.55(dd, J=4.8, J=1.5 Hz, 1H), 8.08 (ddd, J=8.1, 2.0, 2.0 Hz, 1H), 7.32 (dd,J=8.1, 4.8 Hz, 1H), 4.07 (br m, 1H), 3.03 (d, J=5.3 Hz, 3H); ESIMS m/z228.23 (M+2); IR 1540 cm⁻¹.

Example 13 Preparation of2-pyridin-3-yl-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester

To a 20 mL microwave tube was added thionicotinamide (0.552 g, 4.0mmol), ethanol (15 mL) and 2-chloro-4,4,4-trifluoro-3-oxo-butyric acidethyl ester (1.75 g, 8 mmol). The tube was capped and heated in amicrowave at 150° C. for 10 min. The reaction mixture was cooled toambient temperature and Et₃N (1.7 mL, 12 mmol) was added. The tube wascapped and heated in a microwave at 130° C. for 1 min. After cooling toambient temperature the solvent was evaporated and the crude reactionmixture was directly subjected to silica gel chromatography (0 to 100%ethyl acetate/hexanes) to give the desired product as an orange oilwhich subsequently solidified (0.885 g, 73%): IR (KBr) 2988, 1737, 1712cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 9.21 (dd, J=2.5, 0.8 Hz, 1H), 8.77 (dd,J=5.0, 1.7 Hz, 1H), 8.33 (dt, J=8.0, 2.2 Hz, 1H), 7.47 (ddd, J=11.8,4.7, 0.8 Hz, 1H), 4.45 (q, J=14.3, 7.1 Hz, 2H), 1.44 (t, J=7.1 Hz, 3H);ESIMS m/z 303 (M+1).

Example 14 Preparation of2-pyridin-3-yl-4-trifluoromethyl-thiazole-5-carboxylic acid

To a solution of 2-pyridin-3-yl-4-trifluoromethyl-thiazole-5-carboxylicacid ethyl ester (13.9 g, 46 mmol, ca. 85% pure) in methanol (150 mL)was added an aqueous solution of sodium hydroxide (total volume 75 mL,140 mmol), and the mixture was stirred for 40 min. Upon addition of 2 NHCl (70 mL, ca pH=3) to the reaction mixture, a precipitate was formed.Water (300 mL) was then added and the heterogeneous mixture was filteredunder reduced pressure. The precipitate was rinsed further with waterand dried in vacuo to give the desired product as an off-white solid(7.37 g, 58%): mp 209° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.21 (d, J=2.5Hz, 1H), 8.77 (dd, J=4.9, 1.7 Hz, 1H), 8.41 (dt, J=8.0, 1.7 Hz, 1H),7.60 (dd, J=8.0, 4.9 Hz, 1H), 3.4 (br s, 1H); ESIMS m/z 276.2 (M+1).

Example 15 Preparation of(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-carbamic acid tent-butylester (Compound 7)

To 2-pyridin-3-yl-4-trifluoromethyl-thiazole-5-carboxylic acid (6.33 g,23.1 mmol) in toluene/tert-butyl alcohol (100 mL each) was added Et₃N(3.21 mL, 23.1 mmol) and diphenyl phosphoryl azide (5 mL, 23.1 mmol).The reaction mixture was stirred at room temperature for 5 min and thenheated at 95° C. for 4 h. The mixture was cooled to room temperature andthe solvents were removed under reduced pressure. The crude product waspurified by silica gel column chromatography (0 to 100% ethylacetate/hexanes) to give the desired product as a white solid (4.7 g,59%): mp 145-147° C.; ¹H NMR (300 MHz, CDCl₃) δ 9.11 (dd, J=2.5, 0.8 Hz,1H), 8.67 (dd, J=5.0, 1.7 Hz, 1H), 8.22 (ddd, J=8.0, 2.5, 1.7 Hz, 1H),7.58 (br s, 1H), 7.39 (ddd, J=8.0, 4.7, 0.8 Hz, 1H), 1.59 (s, 9H); ESIMSm/z 346.5 (M+1), m/z 344.2 (M-1).

The following compounds were made via the methods in the previousexamples.

(4-Methyl-2-pyrimidin-5-yl-thiazol-5-yl)-carbamic acid tert-butyl ester(Compound 8)

The compound was isolated after purification via silica gel columnchromatography (0 to 100% ethyl acetate/hexanes) to give the desiredproduct as a light yellow solid (0.25 g, 86%): mp 155° C.; ESIMS m/z292.83 (M+1).

(4-Methyl-2-pyridin-3-yl-thiazol-5-yl)-carbamic acid tert-butyl ester(Compound 9)

The compound was isolated after purification via silica gel columnchromatography (0 to 100% ethyl acetate/hexanes) to yield a yellow solid(4.15 g, 61%): mp 146-148° C.; ESIMS m/z 292.5 (M+1).

Example 16 Preparation ofmethyl-(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)carbamic acidtert-butyl ester (Compound 10)

To a solution of(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-carbamic acid tert-butylester (4.7 g, 13.6 mmol) in DMF (70 mL) at 0° C. was added sodiumhydride (NaH, 0.65 g, 16.3 mmol, 60% dispersion in mineral oil) in oneportion and the mixture was stirred for 50 min Iodomethane (0.89 mL,14.3 mmol) was added in one portion, and after 5 min the reactionmixture was warmed to room temperature and stirred for 5.5 h. Water andethyl acetate were added, the resulting biphasic mixture was separatedand the aqueous layer was extracted one time with ethyl acetate. Thecombined organic extracts were washed twice with brine, dried overMgSO₄, filtered and concentrated to dryness under reduced pressure. Thecrude product was purified by silica gel column chromatography (0 to100% ethyl acetate/hexanes) to give the desired product as a clearorange oil (2.72 g, 56%); IR (KBr) 3428, 2981, 1728, 1561 cm⁻¹; ¹H NMR(300 MHz, CDCl₃) δ 9.11 (d, J=2.5 Hz, 1H), 8.72 (dd, J=4.9, 1.1 Hz, 1H),8.26 (dt, J=8.0, 1.7 Hz, 1H), 7.42 (dd, J=8.0, 4.9 Hz, 1H), 3.28 (s,3H), 1.45 (s, 9H); ESIMS m/z 360.6 (M+1).

The following compounds were made via the methods in the previousexamples.

Methyl-(4-methyl-2-pyrimidin-5-yl-thiazol-5-yl)-carbamic acid tert-butylester (Compound 11)

The compound was isolated after purification by silica gel columnchromatography (0 to 100% ethyl acetate/hexanes) to yield a white solid(0.66 g, 75%): ESIMS m/z 307.3 (M+1).

Ethyl-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-carbamic acid tert-butylester (Compound 12)

The compound was isolated after purification via reverse-phasehigh-performance liquid chromatography (CH₃CN/H₂O) to yield an orangeoil (0.16 g, 51%): IR (thin film) 1709 cm⁻¹; ESIMS m/z 320.3 (M+1).

Isopropyl-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-carbamic acidtert-butyl ester (Compound 13)

The compound was isolated after purification via reverse-phasehigh-performance liquid chromatography (CH₃CN/H₂O) to yield a tan solid(0.15 g, 46%): mp 88-89° C.; ESIMS m/z 334.3 (M+1).

Isobutyl-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-carbamic acid tert-butylester (Compound 14)

The compound was isolated after purification via reverse-phasehigh-performance liquid chromatography (CH₃CN/H₂O) to yield a brownsolid (0.13 g, 37%): mp 87-88° C.; ESIMS m/z 348.3 (M+1).

Benzyl-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-carbamic acid tert-butylester (Compound 15)

The compound was isolated after purification via reverse-phasehigh-performance liquid chromatography (CH₃CN/H₂O) to yield a brownsolid (0.25 g, 65%): mp 108-109° C.; ESIMS m/z 382.3 (M+1).

Example 17 Preparation ofmethyl-(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-amine

To a solution of DCE (4 mL) was addedmethyl-(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-carbamic acidtert-butyl ester (0.616 g, 1.7 mmol) and trifluoroacetic acid (4 mL) andthe mixture was stirred for 15 min. The solvents were removed underreduced pressure and the resulting residue was re-dissolved in DCE andaqueous saturated NaHCO₃. The biphasic mixture was separated and theaqueous layer was extracted three times with DCE. The organic extractswere combined, dried over MgSO₄, filtered and concentrated to drynessunder reduced pressure. The crude product was purified by silica gelcolumn chromatography (0 to 100% ethyl acetate/hexanes) to give thedesired product as an off-white solid (0.357 g, 80%): mp 152-157° C.; ¹HNMR (300 MHz, CDCl₃) δ 8.95 (d, J=2.3 Hz, 1H), 8.57 (dd, J=4.9, 1.7 Hz,1H), 8.11 (dt, J=8.2, 2.3 Hz, 1H), 7.23 (ddd, J=7.9, 4.9, 0.7 Hz, 1H),4.83 (br s, 1H), 3.05 (d, J=4.9 Hz, 3H); ESIMS m/z 260 (M+1), m/z 257.9(M-1).

Example 18 Preparation of 2-bromo-4-methyl-thiazole-5-carboxylic acid

To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid ethyl ester(3.0 g, 12 mmol) in tetrahydrofuran (THF, 50 mL) and water (5 mL) wasadded lithium hydroxide hydrate (1.0 g, 24 mmol). The reaction mixturewas stirred at ambient temperature for 16 h. The reaction mixture wasdiluted with water and ethyl acetate. The aqueous layer was made acidicto pH 1 with 2 N hydrochloric acid (HCl) and then was extracted withethyl acetate. The organic extracts were dried over sodium sulfate(Na₂SO₄), filtered and concentrated to provide product as an orangesolid (2.6 g, 98%): mp 152-155° C.; ¹H NMR (300 MHz, CDCl₃) δ 2.74 (s,3H); ESIMS m/z 221 (M-1).

Example 19 Preparation of 2-bromo-4-methyl-thiazole-5-carbonyl-azide

To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (5.0 g,22.5 mmol) in toluene (100 mL) was added Et₃N (2.28 g, 22.5 mmol)followed by diphenyl phosphoryl azide (DPPA, 6.20 g, 22.5 mmol). Thereaction mixture was stirred at ambient temperature for 4 h. Thereaction mixture was concentrated and purified by silica gelchromatography (0-100% ethyl acetate/hexanes) to afford a brown solid(4.67 g, 84%): mp 86-89° C.; IR (KBr) 2183, 1672 cm⁻¹; ¹H NMR (300 MHz,CDCl₃) δ 2.79 (s, 3H); ESIMS m/z 221 ((M−N₂)+2).

Example 20 Preparation of (2-bromo-4-methyl-thiazol-5-yl)-carbamic acidtert-butyl ester

A solution of 2-bromo-4-methyl-thiazole-5-carbonyl-azide (3.0 g, 12.1mmol) in toluene (80 mL) was heated to reflux and stirred for 2 h beforetert-butyl alcohol (2 mL, 20.6 mmol) was added. The reaction mixture wasfurther stirred at reflux for 1 h, then it was cooled and concentrated.Purification by silica gel chromatography (0-100% ethyl acetate/hexanes)afforded an off-white solid (3.4 g, 95%): mp 114-116° C.; ¹H NMR (300MHz, CDCl₃) δ 6.58 (br s, 1H), 2.29 (s, 3H), 1.54 (s, 9H); ESIMS m/z 295(M+2).

Example 21 Preparation of(2-bromo-4-methyl-thiazol-5-yl)-methyl-carbamic acid tert-butyl ester

To a solution of (2-bromo-4-methyl-thiazol-5-yl)-carbamic acidtert-butyl ester (2.93 g, 10 mmol) in DMF (50 mL) at 0° C. was added NaH(480 mg, 12 mmol, 60% dispersion in mineral oil) in one portion and thesuspension was stirred for 1 h. Iodomethane (0.65 mL, 10.5 mmol) wasadded in one portion, and after 5 min the reaction mixture was warmed toambient temperature and stirred for 5 h. Water and ethyl acetate wereadded and the resulting biphasic mixture was separated. The aqueouslayer was extracted one time with ethyl acetate. The combined organicextracts were washed twice with brine, dried over Na₂SO₄, filtered andconcentrated to dryness under reduced pressure. The crude product waspurified by silica gel chromatography (0-100% ethyl acetate/hexanes) togive the desired product as a clear oil (1.66 g, 54%): IR (KBr) 1688cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 2.98 (s, 3H), 2.29 (s, 3H), 1.54 (s,9H); ESIMS m/z 309 (M+2).

Example 22 Preparation of[2-(6-chloropyridin-3-yl)-thiazol-5-yl]-methyl-carbamic acid tert-butylester (Compound 16)

To a suspension of 6-chloro-3-pyridine boronic acid (158 mg, 1.0 mmol)in toluene (4 mL) was added absolute ethanol (2 mL) followed by a 2.0 Msolution of K₂CO₃ (1.0 mL). To this mixture was added(2-bromo-thiazol-5-yl)-methyl-carbamic acid tert-butyl ester (322 mg,1.1 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (58 mg,0.05 mmol). The reaction mixture was heated to 100° C. for 16 h. Themixture was cooled and diluted with ethyl acetate. The organic layer waswashed with saturated aqueous NaHCO₃, dried over Na₂SO₄, filtered andconcentrated. The organic layer was purified by silica gelchromatography (0-100% ethyl acetate/hexanes) to afford an off-whitesolid (270 mg, 83%): mp 167-170° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.88 (brs, 1H), 8.16 (dd J=3.0, 8.0 Hz, 1H), 7.40 (d, J=7.0 Hz, 1H), 7.39 (s,1H), 3.45 (s, 3H), 1.61 (s, 9H); ESIMS m/z 326 (M+1).

The following compound was made according to the procedure in Example22.

N-[2-(5-chloropyridin-3-yl)-4-methyl-thiazol-5-yl]-2-methyl-3-methylsulfanyl-propionamide(Compound 17)

The compound was isolated after purification via silica gelchromatography (0-100% ethyl acetate/hexanes) to afford a viscous brownoil (74 mg, 43%): IR (KBr) 3283, 2968, 2917, 1667, 1562 cm⁻¹; ¹H NMR(300 MHz, CDCl₃) δ 8.96 (d, J=2.0 Hz, 1H), 8.58 (br s, 1H), 8.56 (d,J=2.0 Hz, 1H), 8.22 (t, J=2.0 Hz, 1H), 2.88 (m, 1H), 2.78 (m, 2H), 2.51(s, 3H), 2.23 (s, 3H), 1.40 (d, J=6.0 Hz, 3H); ESIMS m/z 342 (M+1).

Example 23 Preparation of[2-(6-chloropyridin-3-yl)-thiazol-5-yl]-methyl-amine

To a solution of [2-(6-chloropyridin-3-yl)-thiazol-5-yl]-methyl-carbamicacid tert-butyl ester (90 mg, 0.27 mmol) in CH₂Cl₂ (2 mL) was addedtrifluoroacetic acid (2 mL), and the reaction mixture was stirred for 1h at ambient temperature. The reaction was quenched with saturatedaqueous NaHCO₃ and extracted with CH₂Cl₂. The organic layer was driedover Na₂SO₄, filtered, concentrated and purified by silica gelchromatography (0-100% ethyl acetate/hexanes) to afford a yellow oil (50mg, 80%): IR (KBr) 2924, 1591, 1498 cm⁻¹; ¹H NMR 300 MHz, CDCl₃) δ 8.71(d, J=3.0 Hz, 1H), 8.00 (dd J=3.0, 8.0 Hz, 1H), 7.31 (d, J=7.0 Hz, 1H),7.30 (s, 1H), 4.28 (br s, 1H), 3.05 (d, J=8.0 Hz, 3H); ESIMS m/z 226(M+1).

Example 24 Preparation of 4-methyl-2-pyridin-3-yl-thiazol-5-ylamine

To (4-methyl-2-pyridin-3-yl-thiazol-5-yl)-carbamic acid tert-butyl ester(3.73 g, 12.8 mmol) in methanol (100 mL) at 0° C. was slowly addedacetyl chloride (28 mL, 400 mmol). The flask was stoppered and removedfrom the ice bath. The reaction mixture was allowed to warm to ambienttemperature and was stirred overnight. The resulting yellowheterogeneous solution was poured slowly into a separatory funnelcontaining ethyl acetate and saturated aqueous NaHCO₃. When the additionwas complete, more saturated aqueous NaHCO₃ was added until the pH=7.The layers were separated, and the aqueous layer was extracted twicewith ethyl acetate. The combined organic extracts were washed withbrine, dried over MgSO₄, filtered, and concentrated under reducedpressure. The residue was purified via normal phase chromatography (0 to100% ethyl acetate/hexanes) to afford the amino-thiazole as a yellowsolid (1.66 g, 68%): mp 160-162° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.96 (d,J=2.3 Hz, 1H), 8.58 (dd, J=5.0, 1.7 Hz, 1H), 8.06 (dt, J=7.9, 2.3 Hz,1H), 7.30 (dd, J=7.9, 5.0 Hz, 1H), 3.57 (br s, 2H), 2.32 (s, 3H); ESIMSm/z 192 (M+1).

Example 25 Preparation ofN-(2-bromo-4-methyl-thiazol-5-yl)-2-methyl-3-methylsulfanyl-propionamide

To a solution of (2-bromo-4-methyl-thiazol-5-yl)-carbamic acidtert-butyl ester (3.1 g, 10.57 mmol) in DCE (50 mL) was added Et₃N (3.7mL, 26.4 mmol) followed by 2-methyl-3-methylsulfanyl-propionyl chloride(2.42 g, 15.8 mmol). The reaction mixture was heated to 65° C. for 3 h.The mixture was cooled, diluted with DCE, washed with saturated aqueousammonium chloride (NH₄Cl) and dried over Na₂SO₄. The crude product wasdissolved in CH₂Cl₂ (30 mL) and trifluoroacetic acid (10 mL) was added.The reaction mixture was stirred at ambient temperature for 30 min. Thereaction was quenched with saturated aqueous NaHCO₃ and extracted withCH₂Cl₂. The organic layer was dried over Na₂SO₄, filtered, concentratedand purified by silica gel chromatography (0-100% ethyl acetate/hexanes)to afford a clear oil (2.68 g, 82%): IR (KBr) 3282, 2966, 2916, 1668cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 9.97 (br s, 1H), 4.17 (m, 3H), 3.79 (s,3H), 3.59 (s, 3H), 2.76 (d, J=7.0 Hz, 3H); ESIMS m/z 311 (M+2).

Example 26 Preparation ofN-[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-2,2,N-trimethyl-3-methylsulfanyl-propionamide(Compound 18)

To a solution of2,2,2-trifluoro-N-[2-(5-fluoro-pyridin-3-yl)-thiazol-5-yl]-N-methyl-acetamide(244 mg, 0.80 mmol) in methanol (6 mL) was added an aqueous solution ofsodium hydroxide (160 mg, 4 mmol, in 3 mL H₂O), and the mixture wasstirred at room temperature for 45 min. To this solution was added pH7.0 aqueous buffer and ethyl acetate. The layers were separated, and theaqueous layer was extracted with ethyl acetate. The combined organicextracts were dried over MgSO₄, filtered, and concentrated in vacuo. Tothis crude material was added DCE (5 mL), 4-dimethylaminopyridine (DMAP,300 mg, 2.5 mmol) and then a solution of the2,2-dimethyl-3-methylthiopropionyl chloride (250 mg, 1.5 mmol) in DCE(3.0 mL). This mixture was heated to 75° C. and stirred overnight. Theheterogeneous mixture thus obtained was loaded directly onto achromatographic column Silica gel chromatography (0 to 100% ethylacetate/hexanes) afforded the product as a red solid (161 mg, 59%): mp98-102° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.95 (app s, 1H), 8.51 (d, J=2.8Hz, 1H), 7.98 (app dt, J=9.3, 2.5 Hz, 1H), 7.66 (s, 1H), 3.59 (s, 3H),2.87 (s, 3H), 2.17 (s, 2H), 1.47 (s, 6H); ESIMS m/z 340 (M+1).

Example 27 Preparation ofN-methyl-3-methylsulfanyl-N-(2-pyridin-3-yl-thiazol-5-yl)-propionamide(Compound 19)

A solution of 3-methylsulfanyl-propionyl chloride (120 mg, 0.9 mmol) inDCE (1 mL) was pipetted at a dropwise rate into an ice-cold suspensionof methyl-(2-pyridin-3-yl-thiazol-5-yl)-amine (114 mg, 0.6 mmol) in DCE(5 mL), and the mixture was stirred for 5 min before adding a solutionof DMAP (80 mg, 0.6 mmol) in DCE (1 mL). The ice bath was removed after30 min, and the mixture was stirred at reflux under nitrogen for 15 min.The reaction mixture was cooled, diluted with DCE (70 mL), washed withsaturated aqueous NaHCO₃ (50 mL), dried over MgSO₄ and purified bysilica gel chromatography (3:1 ethyl acetate/hexanes) to afford a fineyellow powder (131 mg, 75%): mp 116-118° C.; ¹H NMR (400 MHz, DMSO-d₆) δ9.08 (d, J=2.0 Hz, 1H), 8.61 (dd, J=4.8, 1.4 Hz, 1H), 8.24 (dt, J=9.8,1.8 Hz, 1H), 7.81 (s, 1H), 7.51 (dd, J=7.7, 4.7 Hz, 1H), 3.56 (s, 3H),3.02 (t, J=7.0 Hz, 2H), 2.76 (t, J=7.2 Hz, 2H), 2.12 (s, 3H); ESIMS m/z294 (M+1).

Example 28N-[2-(6-fluoropyridin-3-yl)-4-methyl-thiazol-5-yl]-2,2-dimethyl-3-methylsulfanyl-propionamide(Compound 20)

To a solution of[2-(6-fluoropyridin-3-yl)-4-methyl-thiazol-5-yl]-carbamic acidtert-butyl ester (170 g, 0.55 mmol) in DCE (2.5 mL) was added Et₃N (0.19mL, 1.37 mmol), followed by 2,2-dimethyl-3-methylsulfanyl-propionylchloride (140 mg, 0.82 mmol). The reaction mixture was heated to 65° C.for 16 h. The mixture was cooled, diluted with DCE, washed withsaturated aqueous NaHCO₃ and dried over Na₂SO₄. The crude product wasdissolved in CH₂Cl₂ (2 mL), and trifluoroacetic acid (1 mL) was added.The reaction mixture was stirred at ambient temperature for 30 min. Thereaction was quenched with saturated aqueous NaHCO₃ and extracted withCH₂Cl₂. The organic layer was dried over Na₂SO₄, filtered andconcentrated. Silica gel chromatography (0-100% ethyl acetate/hexanes)afforded a yellow oil (142 mg, 76%): IR (KBr) 3284, 2969, 2918, 1668,1562, 1498 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 8.89 (bs, 1H), 8.72 (d, J=2.0Hz, 1H), 8.27 (dt, J=8.0, 2.0 Hz, 1H), 6.99 (dd, J=8.0, 3.0 Hz 1H), 2.88(s, 2H), 2.51 (s, 3H), 2.24 (s, 3H), 1.45 (s, 6H); ESIMS m/z 340 (M+1).

The following molecule, Compound 21, and Compounds 22-65 and 67-71 inTable 1 were made using the procedures disclosed above.

N-isobutyryl-N-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-isobutyramide(Compound 21)

The compound was isolated after purification by silica gelchromatography (0-100% ethyl acetate/hexanes) as a yellow oil (150 mg,90%): IR (KBr) 2974, 1721 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 9.13 (d, J=2.0Hz, 1H), 8.69 (dd, J=5.0, 3.0 Hz, 1H), 8.21 (dt, J=12.0, 2.0 Hz, 1H),7.42 (dd, J=8.0, 5.0 Hz, 1H), 3.24 (septet, J=7.0 Hz, 2H), 2.32 (s, 3H),1.24 (d, J=7.0 Hz, 12H); ESIMS m/z 332 (M+1).

Example 29 Preparation of[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-1-methyl-3-(2-methylsulfanyl-ethyl)urea(Compound 72)

To a solution of [2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-methyl-amine(0.4 g, 1.91 mmol) in DCE (5 mL) at 0° C. was added phosgene (1.3 mL,2.5 mmol, 20 wt % solution in toluene). After 5 min, DMAP (0.5 g, 4.1mmol) was added in one portion and the ice bath was removed. Afteranother 5 min, the mixture was heated to reflux and stirred for 20 min.The reaction was cooled to ambient temperature and half of the solutionwas transferred to a vial and to this was added 2-(methylthio)ethanamine(0.183 g, 2.0 mmol) and DMAP (0.244 g, 2.0 mmol). The reaction wascapped and heated at 80° C. overnight. The reaction was quenched uponaddition of ethyl acetate and 0.1 N HCl. The layers were separated, andthe organic layer was washed separately with saturated aqueous NaHCO₃and brine. The ethyl acetate layer was dried over MgSO₄, filtered andconcentrated under reduced pressure. The crude product was purified bysilica gel column chromatography (0 to 100% ethyl acetate/hexanes) togive the desired product as an off-white solid (0.253 g, 81%): mp117-119° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.94 (br s, 1H), 8.50 (d, J=2.7Hz, 1H), 7.99-7.94 (m, 1H), 7.54 (s, 1H), 5.37 (m, 1H), 3.53 (q, J=11.8,5.5 Hz, 2H), 3.43 (s, 3H), 2.72 (app t, J=6.6 Hz, 2H), 2.13 (s, 3H);ESIMS m/z 327.1 (M+H); m/z 325.0 (M-1).

The following molecule, Compound 73, was made using the proceduresdisclosed in Example 29.

3-sec-Butyl-1-[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-1-methyl-urea(Compound 73)

The compound was isolated after purification via silica gelchromatography (0 to 100% ethyl acetate/hexanes) to yield a yellow solid(0.07 g, 42%): mp 159-161° C.; ESIMS m/z 309 (M+1).

Example 30 Preparation of[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-1,3-dimethyl-3-(2-methylsulfanyl-ethyl)urea(Compound 74)

To a solution of[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-1-methyl-3-(2-methylsulfanyl-ethyl)urea(173 mg, 0.53 mmol) in DMF (5 mL) cooled to 0° C. was added NaH (26 mg,0.65 mmol, 60% dispersion in mineral oil) and the mixture was stirredfor 30 min. To this was added iodomethane (47 μL, 0.75 mmol) and thereaction mixture was stirred for 1 h. The reaction was quenched byaddition of ethyl acetate and 1 N HCl. The layers were separated, andthe ethyl acetate layer was washed three times with water and once withbrine, dried over MgSO₄, filtered and concentrated to dryness underreduced pressure to give the desired product as a yellow solid (0.110 g,61%): mp 68-69° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.90 (s, 1H), 8.47 (d,J=2.8 Hz, 1H), 7.93 (dt, J=9.3, 2.2 Hz, 1H), 7.45 (s, 1H), 3.54 (t,J=6.9 Hz, 2H), 3.41 (s, 3H), 2.94 (s, 3H), 2.74 (t, J=7.1 Hz, 2H), 2.16(s, 3H); ESIMS m/z 341.1 (M+1).

Example 31 Preparation of[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-methyl-carbamic acid2-methylsulfanyl-ethyl ester (Compound 75)

The carbamoyl chloride was formed as in Example 29. A 0.72 mmol solutionof carbamoyl chloride in DCE was added to 2-(methylthio)ethanol (0.092g, 1.0 mmol) and DMAP (0.122 g, 1.0 mmol) and heated at refluxovernight. The reaction was quenched upon addition of ethyl acetate and0.1 N HCl. The layers were separated, and the organic layer was washedwith saturated aqueous NaHCO₃ and brine. The ethyl acetate layer wasdried over MgSO₄, filtered and concentrated to dryness under reducedpressure. The crude product was purified by silica gel columnchromatography (0 to 100% ethyl acetate/hexanes) to give the desiredproduct as a tan solid (0.102 g, 65%): mp 115-117° C.; ¹H NMR (300 MHz,CDCl₃,) δ 8.90 (s, 1H), 8.46 (d, J=2.6 Hz, 1H), 7.92 (dt, J=9.2, 2.6 Hz,1H), 7.45 (br s, 1H), 4.44 (t, J=6.9 Hz, 2H), 3.49 (s, 3H), 2.83 (t,J=6.6 Hz, 2H), 2.18 (s, 3H); ESIMS m/z 328.1 (M+1).

Compounds 76-77 were made using the procedures disclosed above.

[2-(5-Fluoropyridin-3-yl)-thiazol-5-yl]-methyl-carbamic acid ethyl ester(Compound 76)

The compound was isolated after purification via silica gelchromatography (0 to 100% ethyl acetate/hexanes) to yield an off-whitesolid (0.067 g, 45%): mp 122-124° C.; ESIMS m/z 282.1 (M+1).

[2-(5-Fluoropyridin-3-yl)-thiazol-5-yl]-methyl-carbamic acid5-nitro-furan-2-ylmethyl ester (Compound 77)

The compound was isolated after purification via silica gelchromatography (0 to 100% ethyl acetate/hexanes) to yield a brown solid(0.025 g, 28%): mp 95-99° C.; ESIMS m/z 379.1 (M+1).

Example 32 Preparation ofN-[2-(5-fluoropyridin-3-yl)-thiazol-5-yl]-3-methanesulfinyl-N-methyl-propionamide(Compound 78)

ToN-[2-(5-fluoro-pyridin-3-yl)-thiazol-5-yl]-N-methyl-3-methylsulfanyl-propionamide(Compound 30, 44 mg, 0.14 mmol) in glacial acetic acid (1.5 mL) wasadded sodium perborate tetrahydrate (23 mg, 0.14 mmol), and the mixturewas heated at 65° C. for 2 h. The reaction mixture was carefully pouredinto a separatory funnel containing saturated aqueous NaHCO₃ resultingin gas evolution. When the gas evolution had ceased, DCE was added andthe layers were separated. The aqueous layer was extracted twice withDCE, and all the organic layers were combined, dried over MgSO₄,filtered and concentrated under reduced pressure to give the desiredproduct as white solid (20 mg, 45%): mp 152-154° C.; ¹H NMR (300 MHz,CDCl₃) δ 8.95 (s, 1H), 8.59 (s, 0.3H), 8.49 (s, 0.7H), 7.98 (d, J=9.3Hz, 1H), 7.73 (s, 0.3H), 7.62 (s, 0.7H), 3.64 (s, 2.1H), 3.36 (s, 0.9H),3.40-2.70 (m, 4H), 2.69 (s, 2.1H), 2.61 (s, 0.9H); ESIMS m/z 328.1(M+1), m/z 326.1 (M-1).

Compounds 79-94 in Table 1 were made using the procedures disclosedabove.

Example 33 Preparation of3-methanesulfonyl-N-methyl-N-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-propionamide(Compound 95)

ToN-methyl-N-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-3-methylsulfanyl-propionamide(Compound 19, 132 mg, 0.43 mmol) in glacial acetic acid (4.0 mL) wasadded sodium perborate tetrahydrate (165 mg, 1.07 mmol), and the mixturewas heated at 65° C. for 16 h. The reaction mixture was carefully pouredinto a separatory funnel containing saturated aqueous NaHCO₃ resultingin gas evolution. When the gas evolution had ceased, dichloromethane wasadded and the layers were separated. The aqueous layer was extractedtwice with dichloromethane, and all the organic layers were combined,dried over MgSO₄, filtered and concentrated under reduced pressure. Thecrude product was purified by silica gel column chromatography (0 to 10%methanol/dichloromethane) to give the desired product as a white oil (77mg, 65%): IR (KBr) 2927, 1675 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 9.10 (d,J=2.0 Hz, 1H), 8.68 (dd, J=4.9, 1.7 Hz, 1H), 8.19 (dt, J=8.2, 2.0 Hz,1H), 7.41 (dd, J=7.9, 4.9 Hz, 1H), 3.41 (t, J=6.9 Hz, 2H), 3.28 (s, 3H),2.96 (s, 3H), 2.77 (t, J=7.3 Hz, 2H), 2.38 (s, 3H); ESIMS m/z 340.2(M+1).

Compounds 96-101 were made using the procedures disclosed above.

Example 34 Preparation of[4-methyl-2-(5-methyl-pyridin-3-yl)-thiazol-5-yl]-(2-methyl-3-methylsulfanyl-propionyl)-carbamicacid tert-butyl ester (Compound 156)

To a solution of[4-methyl-2-(5-methyl-pyridin-3-yl)-thiazol-5-yl]-carbamic acidtert-butyl ester (175 mg, 0.57 mmol) in dichloroethane (3 mL) was addedtriethylamine (0.2 mL, 1.44 mmol) followed by2-methyl-3-methylsulfanyl-propionyl chloride (131 mg, 0.86 mmol). Thereaction mixture was stirred at 65° C. for 16 hrs. The mixture wascooled, diluted with dichloroethane, washed with saturated aqueousNaHCO₃ and dried over Na₂SO₄, filtered and concentrated. The crudeproduct was purified by silica gel chromatography (0 to 100% ethylacetate/hexanes) to afford an orange oil (142 mg, 59%): IR (KBr) 1743,1713 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 8.87 (d, J=2.0 Hz, 1H), 8.48 (s,1H), 8.02 (s, 1H), 4.00-3.87 (m, 1H), 2.94 (dd, J=13.2, 8.3 Hz, 1H),2.58 (dd, J=13.2, 6.1 Hz, 1H), 2.40 (s, 3H), 2.28 (s, 3H), 2.15 (s, 3H),1.45 (s, 9H), 1.35 (d, J=6.8 Hz, 3H); ESIMS m/z 422 (M+1).

Example 35 Preparation of2-methyl-N-[4-methyl-2-(5-methyl-pyridin-3-yl)-thiazol-5-yl]-3-methylsulfanyl-propionamide(Compound 171)

To a solution of[4-methyl-2-(5-methyl-pyridin-3-yl)-thiazol-5-yl]-(2-methyl-3-methylsulfanyl-propionyl)-carbamicacid tert-butyl ester (117 mg, 0.27 mmol) in dichloromethane (2 mL) wasadded trifluoroacetic acid (0.6 mL) and the reaction was stirred for 30minutes at ambient temperature. The reaction was quenched with saturatedaqueous NaHCO₃ and the mixture was extracted with dichloromethane. Theorganic layer was dried over Na₂SO₄, filtered and concentrated. Thecrude product was purified by silica gel chromatography (0 to 100% ethylacetate/hexanes) to afford a yellow gum (75 mg, 85%): IR (KBr) 2973,2920, 1711 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 8.89 (d, J=1.9 Hz, 1H), 8.43(s, 1H), 8.00 (s, 1H), 2.91-2.69 (m, 3H), 2.47 (d, J=1.6 Hz, 3H), 2.39(d, J=0.5 Hz, 3H), 2.19 (s, 3H), 2.13 (s, 1H), 1.37 (d, J=6.6 Hz, 3H);ESIMS m/z 322 (M+1).

Example 36 Benzoic acid[(2-methyl-3-methylsulfanyl-propionyl)-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-amino]-methylester (Compound 203)

To a solution of2-methyl-N-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-(3-methylsulfanyl-propionamide(200 mg, 0.65 mmol) in DMF (3.2 mL) was added sodium hydride (52 mg, 1.3mmol) and the reaction was stirred for 30 min at ambient temperature. Tothe reaction mixture was added benzoic acid chloromethyl ester (221 mg,1.3 mmol) and the reaction was stirred at ambient temperature for 16 h.The reaction was quenched with saturated aqueous NH₄Cl and the mixturewas extracted with ethyl acetate. The organic layer was dried overNa₂SO₄, filtered and concentrated. The crude product was purified bysilica gel chromatography (0 to 100% ethyl acetate/hexanes) to afford alight yellow oil (48 mg, 16%): IR (KBr) 1722, 1695 cm⁻¹; ¹H NMR (400MHz, CDCl₃) δ 9.10 (s, 1H), 8.68 (d, J=3.6 Hz, 1H), 8.19 (d, J=7.4 Hz,1H), 8.05 (d, J=7.3 Hz, 2H), 7.60 (t, J=7.4 Hz, 1H), 7.47 (t, J=7.7 Hz,2H), 7.40 (dd, J=5.1, 2.2 Hz, 1H), 6.11 (t, J=10.8 Hz, 1H), 5.78 (dd,J=24.2, 9.4 Hz, 1H), 3.01-2.82 (m, 2H), 2.48 (s, 3H), 2.42 (s, 1H), 2.05(t, J=6.3 Hz, 3H), 1.22 (d, J=6.5 Hz, 3H); ESIMS m/z 442 (M+1).

Example 37 Preparation of(4-bromo-2-pyridin-3-yl-thiazol-5-yl)-methyl-carbamic acid tert-butylester (Compound 242)

To a solution of methyl-(2-pyridin-3-yl-thiazol-5-yl)-carbamic acidtert-butyl ester (100 mg, 0.34 mmol) in acetonitrile (2 mL) was addedN-bromosuccinimide (122 mg, 0.68 mmol) in one portion and the reactionmixture was stirred for 1 h. The reaction mixture was concentrated andthe crude product was purified by silica gel chromatography (0 to 100%ethyl acetate/hexanes) to give the desired product as a white solid (81mg, 64%): mp 88-91°C.; IR (KBr) 1715 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ9.11 (s, 1H), 8.70 (d, J=4.2 Hz, 1H), 8.28-8.17 (m, 1H), 7.42 (dd,J=8.1, 4.8 Hz, 1H), 3.27 (s, 3H), 1.48 (s, 9H); ESIMS m/z 372 (M+2).

Example 38 Preparation of tert-butyl2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-yl carbamate (Compound 481)

To a solution of tert-butyl2-(5-fluoropyridin-3-yl)thiazol-5-ylcarbamate (1.50 g, 5.08 mmol) inacetonitrile (50 mL) at 0° C. was added N-iodosuccinimide (2.40 g, 10.67mmol). The mixture was stirred at 0° C. for 5 min and diluted with ethylacetate and water. The organic phase was separated and rinsed withbrine, dried over MgSO₄ and concentrated in vacuo to give a dark solid.This solid was passed through a bed of silica gel (100g) eluting with10% ether in hexanes (600 mL) to give tert-butyl2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-ylcarbamate as a pale yellowsolid (1.80 g, 84% yield): mp 148-149° C.; ¹H NMR (300 MHz, CDCl₃) δ8.87 (t, J=1.5 Hz, 1H), 8.47 (d, J=2.7 Hz, 1H), 7.93 (ddd, J=9.0, 2.5,1.9 Hz, 1H), 7.08 (s, 1H), 1.57 (s, 9H). ESIMS m/z 422.1 (M+1), 420.2(M-1),

Example 39 Preparation of tert-butyl2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-ylmethyl)carbamate (Compound497)

To a solution of tert-butyl2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-ylcarbamate (1.20 g, 2.85 mmol)in DMF (5.7 mL) at 0° C. was added sodium hydride (125 mg, 3.13 mmol,60% oil suspension) and the mixture was stirred at 0° C. for 10 min. Tothe yellow mixture was added iodomethane (0.49 g, 3.42 mmol) and thereaction mixture was stirred at 0° C. for 30 min. The ice-water bath wasremoved and the mixture was stirred for an additional 1 hour. Themixture was acidified with 0.1 N aq. HCl to neutral pH and diluted withethyl acetate (100 mL) and aqueous sodium bicarbonate (5 mL). Theorganic phase was separated and rinsed with brine, dried over MgSO₄,filtered and concentrated in vacuo to give a yellow residue. Thisresidue was purified on silica gel chromatography (6:4 hexane/ethylacetate) to give tert-butyl2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-yl(methyl)carbamate as a paleyellow solid (1.13 g, 91%): mp 70-71° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.87(s, 1H), 8.53 (bs, 1H), 7.99 (d, J=0.9 Hz, 1H), 3.23 (s, 3H), 1.45 (s,9H); ESIMS m/z 436.1 (M+1).

Example 40 Preparation ofN-(4-cyano-2-(5-fluoropyridin-3-yl)thiazol-5-yl)-N-methyl-3-(methylthio)propanamide(Compound 495)

To a nitrogen-purged solution of tert-butyl2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-yl(methyl)carbamate (1.0 g,2.298 mmol) in DMF (8 mL) was added CuCN (288 mg, 3.22 mmol) and themixture was heated in a microwave at 120° C. for 80 min. The mixture wasdiluted with ethyl acetate (75 mL) and successively washed with anaqueous solution (15 mL) of ethylene diamine (5% v/v), and brine, driedover MgSO₄ filtered, and concentrated on a rotary evaporator undervacuum to give a yellow solid,2-(5-fluoropyridin-3-yl)-5-(methylamino)thiazole-4-carbonitrile. Thesolid was used in the preparation ofN-(4-cyano-2-(5-fluoropyridin-3-yl)thiazol-5-yl)-N-methyl-3-(methylthio)propanamide.To a solution of crude2-(5-fluoropyridin-3-yl)-5-(methylamino)thiazole-4-carbonitrile (200 mg,0.83 mmol) in CH₂Cl₂ (2 mL) were added K₂CO₃ (178 mg, 1.28 mmol) and3-(methylthio)propanoyl chloride (130 mg, 0.94 mmol) followed bydimethylaminopyridine (21 mg, 0.17 mmol). The mixture was stirred atroom temperature for 36 h and diluted with ethyl acetate (20 mL) andsaturated aqueous sodium bicarbonate (5 mL). The organic phase wasseparated and washed with brine, dried over MgSO₄ and concentrated invacuo to give a brown gummy residue. This residue was purified by silicagel chromatography (6:4 hexane/ethyl acetate) to giveN-(4-cyano-2-(5-fluoropyridin-3-yl)thiazol-5-yl)-N-methyl-3-(methylthio)propanamideas a pale yellow solid (164 mg, 57% yield): mp 97-98° C.; ¹H NMR (300MHz, CDCl₃) δ 8.98 (bs, 1H), 8.72 (d, J=2.7 Hz, 1H), 8.27 (dt, J=9.6,1.8 Hz, 1H), 2.73 (t, J=7.5 Hz, 2H), 2.62 (t, J=7.62, 2H), 2.09 (s, 3H),2.03 (s, 3H): ESIMS m/z 337.2 (M+1).

Example 41 Preparation of[2-(5-fluoro-pyridin-3-yl)-4-vinyl-thiazol-5-yl]-methyl-carbamicacid-tert-butyl ester (Compound 363)

To a solution of[2-(5-fluoro-pyridin-3-yl)-4-bromo-thiazol-5-yl]-methyl-carbamicacid-tert-butyl ester (100 mg, 0.257 mmol) in anhydrous 1,4-dioxane (1.5mL) was added vinyl tri-butyl tin (163 mg, 0.514 mmol). The solution wasdegassed prior to the addition of bis(triphenylphosphine)palladium(II)chloride (9 mg, 0.012 mmol). The reaction mixture was stirred at 100° C.for 3 hours. The mixture was concentrated and the product was purifiedvia silica gel chromatography (0 to 100% ethyl acetate/hexanes) toafford a yellow oil (55 mg, 64%): IR (KBr) 1675 cm⁻¹; ¹H NMR (300 MHz,CDCl₃) δ 8.89 (d, J=1.5 Hz, 1H), 8.50 (d, J=2.7 Hz, 1H), 7.99 (m, 1H),6.58 (m, 1H), 6.22 (dd, J=14.0, 1.5 Hz, 1H), 5.51 (dd, J=8.0, 1.5 Hz,1H), 3.22 (s, 3H), 1.43 (s, 9H); ESIMS m/z 336 (M+1).

Example 42 Preparation of di(tert-butyl)2-bromo-1,3-thiazol-5-ylimidodicarbonate

To a tetrahydrofuran (THF) (200 mL) solution of(2-bromo-thiazol-5-yl)-carbamic acid tert-butyl ester (19.8 g, 70.9mmol) at 0° C. (ice bath) was added NaH (3.12 g, 78 mmol, 60% dispersionin mineral oil) in one portion. Gas evolution was observed. The reactionwas stirred for 30 minutes. (Boc)₂O (17.0 g, 78 mmol) was added in oneportion. The reaction was stirred for 5 minutes. The reaction vessel waspulled from the cooling bath and the reaction allowed to stir for 30more minutes. Water and ethyl acetate were added to the reactionmixture. The layers were separated and the aqueous layer was extractedethyl acetate (2×). The combined organic layers were dried over MgSO₄,filtered, and concentrated. Silica gel column chromatography (20 to 50%ethyl acetate/hexanes) afforded the final product as a white solid (25.0g, 93% yield): mp 87-89° C.; ¹H NMR (300 MHz, CDCl₃) δ 7.24 (s, 1H),1.48 (s, 18H); ESIMS m/z 379, 381 (M+1).

Example 43 Preparation of di(tert-butyl)2-(5-fluoropyridin-3-yl)-1,3-thiazol-5-ylimidodicarbonate (Compound 277)

To a 3-neck round bottom flask was added fluoropyridine boronic acid(4.55 g, 32.3 mmol), ethanol (54 mL), and aqueous K₂CO₃ solution (27 mL,2.0 M, 53.8 mmol), followed by 50 mL toluene. To this mixture was addeddi(tert-butyl) 2-bromo-1,3-thiazol-5-ylimidodicarbonate (10.2 g, 26.9mmol). Next, tetrakis(triphenylphosphine)palladium(0) (6.2 g, 5.4 mmol)was added in one portion. The flask was fitted with a reflux condenserand was heated to reflux. After 45 minutes, the reaction was cooled inan ice bath and partitioned between aqueous saturated NaHCO₃ and ethylacetate. The layers were separated and the aqueous layer was extractedonce with ethyl acetate. The combined organics were washed once withbrine, dried over MgSO₄, filtered, and then concentrated. This solid wastriturated with 20% ethyl acetate/hexanes. The solids were filtered offand the filtrate evaporated to provide a residue which was purified viasilica gel column chromatography (0 to 100% ethyl acetate/hexanes) toafford the desired product as an off-white solid (7.74 g, 73% yield): mp94-96° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.91 (app t, J=1.3 Hz, 1H), 8.52(d, J=3.0 Hz, 1H), 7.96 (ddd, J=9.2, 3.0, 1.8 Hz, 1H), 7.66 (s, 1H),1.48 (s, 18H); ESIMS m/z 396 (M+1).

Example 44 Preparation of di(tert-butyl)4-fluoro-2-(5-fluoropyridin-3-yl)-1,3-thiazol-5-ylimidodicarbonate

To a degassed solution of di(tert-butyl)2-(5-fluoropyridin-3-yl)-1,3-thiazol-5-ylimidodicarbonate (1.0 g, 2.53mmol) in anhydrous acetonitrile (20 mL) and DMF (10 mL) was added F-TEDA(SELECTFLUOR™) (1.8 g, 5.06 mmol). The reaction mixture was stirred atambient temperature for 7 days. Water was added to the reaction mixtureand the target extracted with ethyl acetate (2×). The organic layer wasdried over sodium sulfate, was filtered and was concentrated. The crudemixture was purified via silica gel chromatography (0-100% ethylacetate/hexanes) to afford a beige solid (860 mg, 82%): mp 143-143° C.;¹H NMR (300 MHz, CDCl₃) δ 8.87 (t, J=1.4 Hz, 1H), 8.54 (d, J=2.7 Hz,1H), 7.91 (ddd, J=8.9, 2.7, 1.8 Hz, 1H), 1.48 (s, 18H); ESIMS m/z 414(M+1).

Example 45 Preparation of[4-fluoro-2-(5-fluoro-pyridin-3-yl)-thiazol-5-yl]-carbamic acidtert-butyl ester (Compound 353)

To a solution of di(tert-butyl)4-fluoro-2-(5-fluoropyridin-3-yl)-1,3-thiazol-5-ylimidodicarbonate (320mg, 0.77 mmol) in DCM (7 mL) was added trifluoroacetic acid (TFA) (0.7mL). The solution was stirred at room temperature for 10 minutes, beforequenched slowly with saturated NaHCO₃ solution. The organic layer wasseparated and the aqueous layer was extracted with dichloromethane(DCM). The combined organic layer was dried over Na₂SO₄, filtered andpurified by silica gel chromatography (0 to 100% ethyl acetate/hexanes)to give product as a pale yellow solid (166 mg, 68%): mp 188-191° C.; ¹HNMR (300 MHz, CDCl₃) δ 8.84 (s, 1H), 8.46 (d, J=2.7 Hz, 1H), 7.85 (ddd,J=9.1, 2.6, 1.7 Hz, 1H), 6.92 (br s, 1H), 1.55 (s, 9H); ESIMS m/z 312(M-1).

Example 46 Preparation of2,3-diethyl-1-methyl-1-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-isothiourea(Compound 471)

A solution of3-ethyl-1-methyl-1-(4-methyl-2-(pyridin-3-yl)thiazol-5-yl)thiourea (70mg, 0.239 mmol) and iodoethane (74.7 mg, 0.479 mmol) in ethanol (5 mL)was heated at 80° C. for 6 h in a sealed tube. Upon cooling the solventwas removed under reduced pressure and the residue purified via silicagel chromatography (0 to 100% ethyl acetate/hexanes) to furnish thetitle compound as a clear oil (30 mg, 39%): ¹H NMR (400 MHz, CDCl₃) δ9.10 (d, J=2.0 Hz, 1H), 8.64 (dd, J=4.6 Hz, 1.4 Hz, 1H), 8.20 (d, J=4.2Hz, 1H), 7.41-7.37 (m, 1H), 3.63 (q, J=7.6 Hz, 2H), 3.22 (s, 3H), 2.72(q, J=7.8 Hz, 2H), 2.38 (s, 3H), 1.28-1.17 (m, 6H); ESIMS m/z 321 (M+1).

Example 47 Preparation of3-cyclopropyl-1-[2-(5-fluoro-pyridin-3-yl)-4-methyl-thiazol-5-yl]-1-methyl-thiourea(Compound 519)

A solution of 2-(5-fluoropyridin-3-yl)-N,4-dimethylthiazol-5-amine (200mg, 0.896 mmol) and isothiocyanatocyclopropane (266 mg, 2.69 mmol) indioxane (10 mL) was heated at 100° C. for 24 h before the solvent wasremoved under reduced pressure. The residue was purified via silica gelchromatography (0 to 100% ethyl acetate/hexanes) to afford the titlecompound as a yellow solid (211 mg, 73%): mp 117-119° C.; ¹H NMR (400MHz, CDCl₃) δ 8.89 (s, 1H), 8.56 (d, J=2.8 Hz, 1H), 7.96 (dt, J=9.2 Hz,2.4 Hz, 1H), 5.91 (br s, 1H), 3.62 (s, 3H), 3.04-2.99 (m, 1H), 2.31 (s,3H), 0.89-0.81 (m, 2H), 0.57-0.48 (m, 2H); ESIMS m/z 323 (M+1).

Example 48 Preparation of ethyl 2-(pyridin-3-yl)thiazole-4-carboxylate

To a suspension of thionicotinamide (30.0 g, 217.1 mmol) in EtOH (400mL) at room temperature was added ethyl bromopyruvate (90% technical,30.6 mL, 219 mmol). The reaction mixture was heated to reflux andstirred for 2.5 days. The reaction mixture was cooled to roomtemperature and the precipitate that formed upon cooling was collectedvia vacuum filtration. The cake was rinsed twice with hexanes. Thissolid was added to a separatory funnel containing ethyl acetate andsaturated aqueous NaHCO₃. The biphasic mixture was separated and theorganic layer was washed with brine, dried over MgSO₄, filtered, andconcentrated in vacuo. The crude product was purified using silica gelchromatography, (0 to 100% ethyl acetate/hexanes) to afford the desiredproduct as a tan solid (24.1 g, 47%): mp 73-75° C.; ¹H NMR (300 MHz,CDCl₃) δ 9.19 (dd, J=2.6, 1.0 Hz, 1H), 8.69 (dd, J=4.6, 1.6 Hz, 1H),8.34 (dt, J=7.9, 1.6 Hz, 1H), 8.22 (s, 1H), 7.41 (ddd, J=7.9, 4.6, 1.0Hz, 1H), 4.47 (q, J=6.9 Hz, 2H), 1.43 (t, J=6.9 Hz, 3H); ESIMS m/z 236.1(M+2).

Example 49 Preparation of ethyl5-bromo-2-(pyridin-3-yl)thiazole-4-carboxylate

A tetrahydrofuran (15 mL) solution of ethyl2-(pyridin-3-yl)thiazole-4-carboxylate (1.17 g, 5.0 mmol) was added to−78° C. solution of potassium bis(trimethylsilyl)amide (12 mL, 6 mmol,0.5 M in toluene) over 2 min. This reaction mixture was allowed to stirfor 1.5 h and then was transferred via canula into a −78° C. solution ofN-bromosuccinimide (1.35 g, 7.5 mmol) in tetrahydrofuran (5 mL). Thismixture was stirred for 5 min and then the reaction vessel was removedfrom the cooling bath and allowed to warm to room temperature over 3 h.The reaction was quenched by pouring into a mixture of ether and water.The layers were separated and the aqueous layer was extracted twice withethyl acetate. The combined organics were dried over MgSO₄, filtered,and the solvent was removed in vacuo. The residue was subjected tosilica gel chromatography (0 to 100% ethyl acetate/hexanes) to give thedesired product as a white solid (824 mg, 52%): ¹H NMR (300 MHz, CDCl₃)δ 9.09 (d, J=2.3 Hz, 1H), 8.71 (dd, J=4.9, 1.3 Hz, 1H), 8.25 (dt, J=8.2,1.7 Hz, 1H), 7.41 (dd, J=7.9, 4.9 Hz, 1H), 4.48 (q, J=7.3 Hz, 2H), 1.46(t, J=7.3 Hz, 3H); ESIMS m/z 315.0 (M+2).

Example 50 Preparation of ethyl5-amino-2-(pyridin-3-yl)thiazole-4-carboxylate

To a round bottom flask containing ethyl5-bromo-2-(pyridin-3-yl)thiazole-4-carboxylate (2.5 g, 7.98 mmol) in DMF(26.6 ml)/water (13.3 ml) was carefully added sodium azide (2.59 g, 39.9mmol) and stirred overnight at 75° C. The reaction was cooled to roomtemperature and poured into water which was extracted with ethylacetate. The ethyl acetate layers were combined and washed withhexanes/water. The ethyl acetate extracts were dried (MgSO₄), filteredand concentrated to dryness. The crude material was purified by silicagel column chromatography (0 to 75% ethylacetate/hexanes) to give thedesired product as a white solid (0.6 g, 30%) ¹H NMR (300 MHz, CDCl₃) δ8.98 (s, 1H), 8.63 (d, 1H), 8.19 (d, 1H), 7.45-7.32 (m, 1H), 6.3 (s,2H), 4.46 (q, 2H), 1.43 (t, 3H). ESIMS m/z 251.1 (M+2).

Example 51 Preparation of3-[cyano(methyl)sulfonimidoyl]-N-[2-(5-fluoropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]-2-methylpropanamide(Compound 163)

To a solution ofN-[2-(5-fluoro-pyridin-3-yl)-4-methyl-thiazol-5-yl]-2-methyl-3-methylsulfanyl-propionamide(0.250 g, 0.76 mmol) in dichloromethane (3.07 ml) at 0° C. was addedcyanamide (0.064 g, 1.53 mmol) and iodobenzenediacetate (0.272 g, 0.84mmol) and subsequently stirred at room temperature for 1 hour. Thereaction was concentrated to dryness. The crude material was purified bysilica gel column chromatography (10% methanol/ethyl acetate) to givethe desired product as a light yellow solid (0.220 g, 60%): mp 75-81°C.; ¹H NMR (400 MHz, CDCl₃) δ 9.85 (s, 1H), 8.94-8.70 (m, 1H), 8.57-8.34(m, 1H), 8.07-7.77 (m, 1H), 3.69-3.40 (m, 2H), 3.22-3.00 (m, 1H),2.92-2.77 (m, 3H), 2.50 (m, 3H), 1.49 (m, 3H); ESIMS m/z 363.9 (M-2).

Example 52-A Preparation of3-[cyano(methyl)sulfonimidoyl]-N-[2-(5-fluoropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]-2-methylpropanamide(Compound 164)

To a solution of 70% mCPBA (0.13 g, 0.61 mmol) in EtOH (2 ml) at 0° C.was added a solution of potassium carbonate (0.17 g, 1.23 mmol) in water(2 ml) and stirred for 20 minutes after which a solution of3-[cyano(methyl)sulfonimidoyl]-N-[2-(5-fluoropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]-2-methylpropanamide(0.15 g, 0.41 mmol) in EtOH (2 ml) was added in one portion. Thereaction was stirred for 1 h at 0° C. The excess mCPBA was quenched with10% Na₂S₂O₃ and the reaction was concentrated to dryness. To the whitesolid was added dichloromethane and the mixture was filtered to removesolids. The filtrate was collected and concentrated to dryness. Thecrude material was purified by silica gel chromatography (100% ethylacetate) to give the desired product as a light yellow solid (0.034 g,22%): ¹H NMR (400 MHz, CDCl₃) δ 8.87 (s, 1H), 8.53 (s, 1H), 8.45 (t,J=4.1 Hz, 1H), 7.93-7.85 (m, 1H), 3.74 (dd, J=14.2, 9.3 Hz, 1H),3.38-3.25 (m, 1H), 3.14 (dd, J=14.2, 3.0 Hz, 1H), 3.01 (s, 3H), 2.47 (s,3H), 1.48 (t, J=7.6 Hz, 3H).

Example 52-B Preparation of2-methyl-N-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-3-methylsulfanyl-thiopropionamide(Compound 180)

To a microwave reaction vessel was added2-methyl-N-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)3-methylsulfanyl-propionamide(0.10 g, 0.32 mmol) in dioxane and Lawesson's reagent (0.19 g, 0.48mmol). The vessel was capped and heated in a Biotage Initiator microwavereactor for 1 min at 130° C., with external IR-sensor temperaturemonitoring from the side. The reaction was concentrated to dryness andthe crude material was purified by silica gel chromatography (0 to 100%ethyl acetate/hexanes) to give the desired product as a yellow semisolid (0.019 g, 18%): ¹H NMR (300 MHz, CDCl₃) δ 9.9 (m, 1H), 9.2 (d,1H), 8.65 (d, 1H), 8.4 (m, 1H), 7.4 (m, 1H), 3.15 (m, 1H), 2.9 (m, 2H),2.5 (s, 3H), 2.2 (s, 3H), 1.5 (d, 3H); ESIMS m/z 324.12 (M+1).

Example 53 Preparation ofN-(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-N-ethyl-2-methyl-3-methylsulfanyl-propionamide(Compound 316)

To a solution of (4-chloro-2-pyridin-3-yl-thiazol-5-yl)-ethylamine (800mg, 3.33 mmol) in dichloroethane (30 mL) was added2-methyl-3-methylsulfanyl-propionic acid (prepared according toliterature reference J. Org. Chem. 1996, 51, 1026-1029) (894 mg, 6.66mmol) and N,N-dimethylaminopyridine (814 mg, 6.66 mmol) followed bytriethylamine (0.2 mL, 1.44 mmol). To this was added1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.92 g,9.99 mmol). The reaction mixture was stirred at ambient temperature for16 h. The reaction mixture was concentrated and the crude product waspurified by silica gel chromatography (0 to 100% ethyl acetate/hexanes)to afford a beige solid (715 mg, 60%): mp 79-81° C.; ¹H NMR (300 MHz,CDCl₃) δ 9.11 (d, J=1.7 Hz, 1H), 8.71 (d, J=4.8 Hz, 1H), 8.27-8.13 (m,1H), 7.42 (dd, J=8.0, 4.9 Hz, 1H), 3.90 (bs, 1H), 3.69 (bs, 1H), 2.80(bs, 2H), 2.47 (bs, 1H), 2.02 (s, 3H), 1.21 (q, J=7.3 Hz, 6H); ESIMS m/z356 (M+1).

Example 54 Preparation of 4-chloro-5-nitro-2-(pyridin-3-yl)thiazole

4-Chloro-2-(pyridin-3-yl)thiazole (1.00 g, 5.09 mmol) was placed in adry flask and concentrated H₂SO₄ (2.50 g, 25.4 mmol) was added. Thecontents were cooled to 0° C., and fuming HNO₃ (641 mg, 10.17 mmol) wasslowly added. The mixture was stirred at 40° C. for 3 h and cooled toroom temperature. The contents were slowly added to an ice-coldsaturated aqueous solution of NaHCO₃. The mixture was extracted withethyl acetate (2×50 mL) and the extracts were combined, rinsed withbrine and concentrated in vacuo to give4-chloro-5-nitro-2-(pyridin-3-yl)thiazole as a peach-colored solid (985mg, 80% yield): mp 110-112° C.; ¹H NMR (300 MHz, CDCl₃) 9.18 (d, J=2.1Hz, 1H), 8.81 (dd, J=5.1, 1.8 Hz, 1H)), 8.27 (ddd, J=7.3, 4.2, 2.4 Hz,1H), 7.49 (dd, J=7.8, 5.1 Hz, 1H); EIMS m/z 241 ([M+H])⁺.

Example 55 Preparation of4-(methylthio)-5-nitro-2-(pyridin-3-yl)thiazole

To a solution of 4-chloro-5-nitro-2-(pyridin-3-yl)thiazole (500 mg, 2.07mmol) in 1,4-dioxane (2 mL) was added in one portion solid sodiumthiomethoxide (145 mg, 2.07 mmol). The orange-red mixture was stirred atroom temperature for 3 hours. The mixture was diluted with ethyl acetateand rinsed with brine, dried over MgSO₄ and concentrated in vacuo togive a yellow solid. This solid was purified by silica gelchromatography (ethyl acetate/hexanes) to give4-(methylthio)-5-nitro-2-(pyridin-3-yl)thiazole (358 mg, 68%): ¹H NMR(300 MHz, CDCl₃) δ 9.21 (d, J=5.4 Hz, 1H), 8.79 (dd, J=4.8, 1.8 Hz, 1H),8.24 (dt, J=7.8, 2.1 Hz, 1H), 7.46 (ddd, J=8.1, 4.8, 0.9 Hz, 1H), 2.81(s, 3H); EIMS m/z 253.

Example 56 Preparation of3-(methylthio)-N-(4-(methylthio)-2-(pyridin-3-yl)thiazol-5-yl)propanamide(Compound 589)

To a nitrogen-purged solution of4-(methylthio)-5-nitro-2-(pyridin-3-yl)thiazole (253 mg, 1 mmol) inethyl acetate (50 mL) in a Parr bottle were added glacial acetic acid(601 mg, 10 mmol), followed by Pd on carbon (35 mg, 10% (w)). Hydrogenwas added and the mixture was shaken in a Parr shaker for 2 hours andfiltered through a bed of Celite®. The filtrate was concentrated undervacuum to give 4-(methylthio)-2-(pyridin-3-yl)thiazol-5-amine as a paleyellow solid, which was placed under high vacuum to remove residualacetic acid. This crude was found to be 95% pure by GC-MS. The crude4-(methylthio)-2-(pyridin-3-yl)thiazol-5-amine was used without furtherpurification to prepare3-(methylthio)-N-(4-(methylthio)-2-(pyridin-3-yl)thiazol-5-yl)propanamide.To a solution of 4-(methylthio)-2-(pyridin-3-yl)thiazol-5-amine (100 mg,0.45 mmol) in methylene chloride (2 mL) were added dimethylaminopyridine(137 mg, 1.12 mmol) followed by 3-(methylthio)propanoyl chloride (68 mg,0.49 mmol). The mixture was stirred at room temperature for 30 min. Themixture was diluted with dichloromethane (10 mL) and water (5 mL). Theorganic phase was separated, rinsed with brine, dried over MgSO₄ andconcentrated in vacuo to give a yellow solid. This solid was purified bysilica gel chromatography (methylene chloride-methanol) to give3-(methylthio)-N-(4-(methylthio)-2-(pyridin-3-yl)thiazol-5-yl)propanamideas a yellow solid (32 mg, 22%): mp 72-74° C., ¹H NMR (300 MHz, DMSO-d₆)δ 10.90 (s, 1H), 9.08 (m, 1H), 8.64 (d, J=4.8 Hz, 1H), 8.32 (d, J=9.0Hz, 1H), 7.57 (dd, J=5.1 Hz, 8.4 Hz, 1H), 3.25 (s, 3H), 2.85 (m, 2H),2.73 (m, 2H), 2.07 (s, 3H); ESIMS m/z 326.1(M+1), 324.1 (M-1).

Example 57 Preparation of 1-(2-methyl-pentanoyl)-piperidine-3-carboxylicacid [2-(5-fluoro-pyridin-3-yl)-4-methyl-thiazol-5-yl]-methyl-amide(Compound 582)

A solution ofN-(2-(5-fluoropyridin-3-yl)-4-methylthiazol-5-yl)-N-methylpiperidine-3-carboxamide(250 mg, 0.75 mmol), DMAP (91 mg, 0.75 mmol), potassium carbonate (310mg, 2.243 mmol), and 2-methylpentanoyl chloride (201 mg, 1.495 mmol) inDCE (10 mL) was heated at 80° C. for 6 h. The cooled contents werediluted with water:dichloromethane (1:1, 20 mL) and the organic layerwas collected and concentrated. The residue was purified via reversedphase chromatography (0 to 100% acetonitrile/water) to furnish the titlecompound as a clear oil (207 mg, 64%): ¹H NMR (400 MHz, CDCl₃) δ 8.89(s, 1H), 8.54 (d, J=2.2 Hz, 1H), 7.96 (dt, J=9.0, 2.2 Hz, 1H), 4.63-4.59(m, 1H), 3.92-3.78 (m, 1H), 3.42 (s, 3H), 2.66-2.48 (m, 4H), 2.38 (s,3H), 1.89-1.73 (m, 2H), 1.71-1.68 (m, 2H), 1.38-1.17 (m, 4H), 1.08-1.01(m, 3H), 0.97-0.86 (m, 3H); ESIMS m/z 433 (M+1).

Example 58 Preparation of(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-ethyl-carbamic acid tert-butylester (Compound 304)

To a suspension of 3-pyridine boronic acid (1.5 g, 12.2 mmol) in toluene(50 mL) was added absolute ethanol (25 mL) followed by a 2.0 M solutionof K₂CO₃ (12.5 mL). To this mixture was added(2-bromo-4-chloro-thiazol-5-yl)-ethyl-carbamic acid tert-butyl ester(4.2 g, 12.2 mmol) followed by tetrakis(triphenylphosphine)palladium(0)(708 mg, 0.61 mmol). The reaction mixture was heated to 100° C. for 16h. The mixture was cooled and diluted with ethyl acetate. The organiclayer was washed with saturated aqueous NaHCO₃, dried over Na₂SO₄,filtered and concentrated. The organic layer was purified by silica gelchromatography (0 to 100% ethyl acetate/hexanes) to afford a red oil(3.3 g, 79%): ¹H NMR (300 MHz, CDCl₃) δ 9.09 (d, J=1.9 Hz, 1H), 8.68(dd, J=4.8, 1.6 Hz, 1H), 8.19 (dd, J=5.9, 4.2 Hz, 1H), 7.39 (dd, J=7.6,5.2 Hz, 1H), 3.68 (q, J=7.2 Hz, 2H), 1.45 (s, 9H), 1.22 (t, J=7.0 Hz,3H); ESIMS m/z 340 (M+1).

Example 59 Preparation of(2-bromo-4-chloro-thiazol-5-yl)-methyl-carbamic acid tert-butyl ester

To a solution of (2-bromo-thiazol-5-yl)-ethyl-carbamic acid tert-butylester (4.0 g, 13 mmol) in acetonitrile (75 mL) was addedN-chlorosuccinimide (3.48 g, 26 mmol) in one portion and the reactionmixture was stirred for 16 h. The reaction mixture was concentrated andthe crude product was purified by silica gel chromatography (0 to 100%ethyl acetate/hexanes) to give the desired product as a grey solid (4.2g, 95%): IR (KBr) 1738 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 3.61 (q, J=7.1Hz, 2H), 1.43 (s, 9H), 1.16 (t, J=7.1 Hz, 3H).

Example 60 Preparation of 2,4-dichloro-thiazole-5-carbonyl-azide

To a solution of 2,4-dichloro-thiazole-5-carboxylic acid (1.98 g, 10mmol) in toluene (50 mL) was added Et₃N (1.01 g, 10 mmol) followed bydiphenyl phosphoryl azide (2.75 g, 10 mmol). The reaction mixture wasstirred at room temperature for 20 h. The reaction mixture wasconcentrated in vacuo and purified by silica gel chromatography (0 to100% ethyl acetate/hexanes) to afford product as a brown solid (1.82 g,82%): ¹³C NMR (75 MHz, CDCl₃) δ 163.33, 156.83, 143.94, 124.02.

Example 61 Preparation of (2,4-dichloro-thiazol-5-yl)-carbamic acidtert-butyl ester

To a 250 mL round bottom flask filled with N₂ was added2,4-dichloro-thiazole-5-carbonyl-azide (1.82 g, 12.1 mmol) and toluene(55 mL). The solution was heated to reflux for 2 h before tert-butylalcohol (1.21 g mL, 16.3 mmol) was added. The reaction mixture was thenrefluxed for 1.5 h, cooled and concentrated in vacuo. Purification bysilica gel chromatography (0 to 100% ethyl acetate/hexanes) gave productas a white solid (2.06 g, 94%): mp 111-112° C.; ¹H NMR (300 MHz, CDCl₃)δ 6.96 (s, 1H), 1.54 (s, 9H).

Example 62 Preparation of(2,4-dichloro-thiazol-5-yl)-(3-methylsulfanyl-propionyl)-carbamic acidtert-butyl ester

To a solution of (2,4-dichloro-thiazol-5-yl)-carbamic acid tert-butylester (1.0 g, 3.7 mmol) in dichloroethane (20 mL) stirring at roomtemperature was added triethylamine (935 mg, 9.25 mmol), followed bydropwise addition of methylsulfanyl-propionyl chloride (776 mg, 5.6mmol) and the mixture was stirred for 5 min before DMAP (45 mg, 0.37mmol) was added. The mixture was stirred at 75° C. for 4 h. The reactionmixture was cooled, quenched with H₂O (30 mL). The organic layer wasseparated and the aqueous layer extracted with dichloromethane (20 mL).The combined organic layer was dried over Na₂SO₄ and purified by silicagel chromatography (0 to 100% ethyl acetate/hexanes) to give product asa colorless oil (1.11 g, 81%): ¹H NMR (300 MHz, CDCl₃) δ 3.32 (t, J=7.3Hz, 2H), 2.83 (t, J=7.3 Hz, 2H), 2.16 (s, 3H), 1.46 (s, 9H); ESIMS m/z371.2 (M+1).

Example 63 Preparation ofN-(2,4-dichloro-thiazol-5-yl)-3-methylsulfanyl-propionamide

To a solution of(2,4-dichloro-thiazol-5-yl)-(3-methylsulfanyl-propionyl)-carbamic acidtert-butyl ester (1.10 g, 2.97 mmol) in DCM (10 mL) was addedtrifluoroacetic acid (3.4 g, 2.2 mL, 30 mmol). The solution was stirredat room temperature for 15 minutes, before it was quenched slowly withsaturated NaHCO₃ solution. The organic layer was separated and theaqueous layer was extracted with 20 mL DCM. The combined organic layerwas dried over Na₂SO₄ and purified by silica gel chromatography (0 to100% ethyl acetate/hexanes) to give product as a white solid (612 mg,76%): ¹H NMR (300 MHz, CDCl₃) δ 8.79 (s, 1H), 2.90 (t, J=7.2 Hz, 2H),2.79 (t, J=7.2 Hz, 2H), 2.29 (s, 3H); ESIMS m/z 271.0 (M+1).

Example 64 Preparation ofN-(2,4-dichloro-thiazol-5-yl)-N-methyl-3-methylsulfanyl-propionamide

To a solution ofN-(2,4-dichloro-thiazol-5-yl)-3-methylsulfanyl-propionamide (596 mg, 2.2mmol) in DMF (11 mL) stirring at 25° C. was added K₂CO₃ (365 mg, 2.64mmol) and iodomethane (375 mg, 1.2 mmol), the solution was stirred at25° C. for 20 h. The solution was diluted with 50 mL H₂O and extractedwith ethyl acetate (3×20 mL). The combined organic extracts were washedwith H₂O (3×20 mL), dried over Na₂SO₄, filtered and concentrated todryness under reduced pressure. The crude product was purified by silicagel chromatography (0 to 100% ethyl acetate/hexanes) to give the desiredproduct as a clear oil (273 mg, 44%): ¹H NMR (300 MHz, CDCl₃) δ 3.23 (s,3H), 2.79 (t, J=7.2 Hz, 2H), 2.52 (t, J=7.2 Hz, 2H), 2.09 (s, 3H); ESIMSm/z 285.1 (M+1).

Example 65 Preparation ofN-[4-chloro-2-(6-fluoro-pyridin-3-yl)-thiazol-5-yl]-N-methyl-3-methylsulfanyl-propionamide(Compound 453)

To a solution ofN-(2,4-dichloro-thiazol-5-yl)-N-methyl-3-methylsulfanyl-propionamide(273 mg, 0.96 mmol) in toluene (4 mL) was added6-fluoropyridine-3-boronic acid (162 mg, 1.15 mmol) and Pd(PPh₃)₄ (56mg, 0.048 mmol), followed by 1 mL 2M K₂CO₃ solution and 2 mL EtOH. Thesolution was deoxygenated by three vacuum-flush cycles under nitrogenand heated in 110° C. oil bath for 8 hours. H₂O (10 mL) was added andthe aqueous layer was extracted with ethyl acetate (2×10 mL). Thecombined organic layer was dried over Na₂SO₄, concentrated in vacuo andpurifid by silica gel chromatography (0 to 100% ethyl acetate/hexanes)to afford product as a colorless oil (131 mg, 75%): ¹H NMR (300 MHz,CDCl₃) δ 8.74 (d, J=2.1 Hz, 1H), 8.48-8.21 (m, 1H), 7.09 (dd, J=8.6, 2.9Hz, 1H), 3.29 (s, 3H), 2.82 (t, J=7.3 Hz, 2H), 2.57 (t, J=7.3 Hz, 2H),2.09 (s, 3H); IR (KBr) 1685; ESIMS m/z 346.2 (M+1).

Example 66 Preparation of(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-methyl-carbamic acid tert-butylester (Compound 228)

To a solution of methyl-(2-pyridin-3-yl-thiazol-5-yl)-carbamic acidtert-butyl ester (3.0 g, 10.29 mmol) in acetonitrile (60 mL) was addedN-chlorosuccinimide (2.75 g, 20.58 mmol) in one portion and the reactionmixture was stirred at 45° C. for 16 h. The reaction mixture wasconcentrated and the crude product was purified by silica gelchromatography (0 to 100% ethyl acetate/hexanes) to give the desiredproduct as a yellow solid (2.10 g, 62%): mp 119-122° C.; IR (KBr) 1718cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 9.08 (s, 1H), 8.67 (d, J=4.2 Hz, 1H),8.22-8.16 (m, 1H), 7.39 (dd, J=7.9, 5.0 Hz, 1H), 3.26 (s, 3H), 1.46 (s,9H); ESIMS m/z 326 (M+1).

Example 67 Preparation of(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-methyl-amine

To a solution of (4-chloro-2-pyridin-3-yl-thiazol-5-yl)-methyl-carbamicacid tert-butyl ester (0.072 g, 0.22 mmol) in dichloromethane (1 mL) wasadded thiophenol (34 μL, 0.33 mmol) followed by trifluoroacetic acid (1mL). The reaction was stirred for 30 minutes at ambient temperature. Thereaction was quenched with saturated aqueous NaHCO₃ and the mixture wasextracted with dichloromethane. The organic layer was dried over Na₂SO₄,filtered and concentrated. The crude product was purified by silica gelchromatography (0 to 100% ethyl acetate/hexanes) to afford a brightyellow solid (0.048 g, 98%): mp 79° C.; IR (KBr) 1540 cm⁻¹; ¹H NMR (400MHz, CDCl₃) δ 8.97 (d, J=2.1 Hz, 1H), 8.55 (dd, J=4.8, J=1.5 Hz, 1H),8.08 (ddd, J=8.1, 2.0, 2.0 Hz, 1H), 7.32 (dd, J=8.1, 4.8 Hz, 1H), 4.07(br m, 1H), 3.03 (d, J=5.3 Hz, 3H); ESIMS m/z 226 (M+1).

Example 68 Preparation ofN-(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-N-methyl-3-methylsulfanyl-propionamide(Compound 66)

To a solution of (4-chloro-2-pyridin-3-yl-thiazol-5-yl)-methylamine (49mg, 0.21 mmol) in dichloroethane (2 mL) was addedN,N-dimethylaminopyridine (39 mg, 0.32 mmol) followed by3-methylsulfanyl-propionyl chloride (45 mg, 0.32 mmol). The reactionmixture was stirred at ambient temperature for 16 hours. The reactionwas diluted with saturated aqueous NaHCO₃ and the mixture was extractedwith dichloromethane. The organic layer was dried over Na₂SO₄, filteredand concentrated. The crude product was purified by silica gelchromatography (0 to 100% ethyl acetate/hexanes) to afford a pale yellowgum (52 mg, 73%): IR (KBr) 1682 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 9.11 (s,1H), 8.73 (d, J=3.4 Hz, 1H), 8.28-8.14 (m, 1H), 7.43 (dd, J=8.2, 5.0 Hz,1H), 3.28 (s, 3H), 2.81 (t, J=7.2 Hz, 2H), 2.56 (t, J=7.2 Hz, 2H), 2.08(s, 3H); ESIMS m/z 328 (M+1).

Example 69 Preparation ofN-(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-2,N-dimethyl-3-methylsulfanyl-propionamide(Compound 227)

To a solution of (4-chloro-2-pyridin-3-yl-thiazol-5-yl)-methylamine (200mg, 0.88 mmol) in dichloroethane (2 mL) was added pyridine (83 mg, 1.05mmol), N,N-dimethylaminopyridine (54 mg, 0.44 mmol) followed by2-methyl-3-methylsulfanyl-propionyl chloride (160 mg, 1.05 mmol). Thereaction mixture was stirred at ambient temperature for 16 hours. Thereaction was diluted with water and the mixture was extracted withdichloromethane. The organic layer was dried over Na₂SO₄, filtered andconcentrated. The crude product was purified by silica gelchromatography (0 to 100% ethyl acetate/hexanes) to afford a lightyellow solid (250 mg, 84%): mp 70-73° C.; ¹H NMR (300 MHz, CDCl₃) δ 9.14(s, 1H), 8.75 (d, J=3.8 Hz, 1H), 8.28-8.15 (m, 1H), 7.45 (dd, J=8.0, 4.9Hz, 1H), 3.32 (s, 3H), 2.99-2.72 (m, 2H), 2.50 (d, J=7.5 Hz, 1H), 2.06(d, J=2.5 Hz, 3H), 1.31-1.14 (m, 3H); ESIMS m/z 342 (M+1).

Example 70 Preparation of(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-ethyl-carbamic acid tert-butylester (Compound 304)

To a solution of ethyl-(2-pyridin-3-yl-thiazol-5-yl)-carbamic acidtert-butyl ester (3.0 g, 9.82 mmol) in acetonitrile (58 mL) was addedN-chlorosuccinimide (2.62 g, 19.64 mmol) in one portion and the reactionmixture was stirred at 45° C. for 16 h. The reaction mixture wasconcentrated and the crude product was purified by silica gelchromatography (0 to 100% ethyl acetate/hexanes) to afford a red oil(2.24 g, 67%): ¹H NMR (300 MHz, CDCl₃) δ 9.09 (d, J=1.9 Hz, 1H), 8.68(dd, J=4.8, 1.6 Hz, 1H), 8.19 (dd, J=5.9, 4.2 Hz, 1H), 7.39 (dd, J=7.6,5.2 Hz, 1H), 3.68 (q, J=7.2 Hz, 2H), 1.45 (s, 9H), 1.22 (t, J=7.0 Hz,3H); ESIMS m/z 340 (M+1).

Example 71 Preparation of(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-ethyl-amine hydrochloride

Into a 1 L three-necked flask fitted with a J-KEM type-T temperatureprobe, overhead stirrer, and nitrogen inlet was added(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-ethyl-carbamic acid tert-butylester (63.5 g, 187 mmol) and 1,4-dioxane (125 mL). To the solution wasadded 4 M HCl/dioxane (100 mL, 400 mmol). The mixture exothermed from31° C. to 49° C. over 10 seconds and slowly turned from an auburnsolution to a green-black solution. After 10 minutes the reaction hadcooled back to 25° C. After 30 min a green-yellow precipitate began toform in the reaction mixture. The reaction conversion was 31% after 10min, 32% after 1.5 hours and 67% after 16 hours. Additional 4MHCl/dioxane (75 mL, 300 mmol) was added (note: no exotherm this time)and the reaction stirred at 23° C. for 1.5 hours (no change in reactionprogress by HPLC analysis). The reaction was heated to 40° C. for 4hours which led to complete conversion. The reaction was allowed to coolto 25° C. and ether (200 mL) was added. The green-yellow suspension wasstirred for 30 min and the solid collected by vacuum filtration andwashed with ether (2×50 mL). This gave a green-yellow filter cake whichwas allowed to stand in the air for 16 hours. This gave 67.99 g (131%)of a green-yellow wet cake that assayed to >99% purity by HPLC at 254nm. The sample was placed into a vacuum oven (55° C., 74 mmHg vacuum, 4hours). This gave 53.96 g (quantitative yield) of a green solid: mp180-182 C; ¹H NMR (400 MHz, DMSO-d₆) δ 9.08 (d, J=2.1 Hz, 1H), 8.75 (dd,J=5.5, 0.9 Hz, 1H), 8.66 (ddd, J=8.3, 2.2, 1.3 Hz, 1H), 7.97 (ddd,J=8.3, 5.5, 0.6 Hz, 1H), 3.21 (q, J=7.1 Hz, 2H), 2.51 (dt, J=3.7, 1.8Hz, 1H), 1.24 (dd, J=9.2, 5.1 Hz, 3H); ESIMS m/z 240 (M+1).

Example 72 Preparation ofN-(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-N-ethyl-3-methylsulfanyl-propionamide(Compound 313)

To a solution of (4-chloro-2-pyridin-3-yl-thiazol-5-yl)-ethylaminehydrochloride (275 mg, 1.0 mmol) in dichloroethane (2 mL) was addedN,N-dimethylaminopyridine (305 mg, 2.5 mmol) followed by3-methylsulfanyl-propionyl chloride (180 mg, 1.3 mmol). The reactionmixture was stirred at ambient temperature for 16 hours. The reactionwas diluted with saturated aqueous NaHCO₃ and the mixture was extractedwith dichloromethane. The organic layer was dried over Na₂SO₄, filteredand concentrated. The crude product was purified by silica gelchromatography (0 to 100% ethyl acetate/hexanes) to afford a yellow oil(298 mg, 87%): IR (KBr) 1680 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ 9.11 (s,1H), 8.73 (d, J=3.4 Hz, 1H), 8.28-8.14 (m, 1H), 7.43 (dd, J=8.2, 5.0 Hz,1H), 3.77 (br s, 2H), 2.81 (t, J=7.2 Hz, 2H), 2.56 (t, J=7.2 Hz, 2H),2.08 (s, 3H), 1.21 (t, J=7.2 Hz, 3H); ESIMS m/z 342 (M+1).

Example 73 Preparation ofN-(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-N-ethyl-2-methyl-3-methylsulfanyl-propionamide(Compound 316)

Into a 500-mL three-necked flask fitted with a J-KEM type-T temperatureprobe, overhead stirrer, reflux condensor, and nitrogen inlet was added(4-chloro-2-pyridin-3-yl-thiazol-5-yl)-ethyl-amine hydrochloride (20.0g, 72.4 mmol green solid) and dichloromethane (150 mL). To thissuspension was added pyridine (14.32 g, 181 mmol, 2.5 eq) (portionwiseover 1 min to form a dark green-black solution. To this solution wasadded DMAP (4.4 g, 36 mmol) followed by 2-methyl-3-methylthiopropanoylchloride (16.5 g, 108.6 mmol), which was added portionwise over 1minute. The reaction exotherm went from 20° C. to 31° C. during theaddition of the acid chloride. The reaction was heated to 35° C. for 10hours then cooled to 25° C. for 14 h. To the dark brown reaction mixturewas added dichloromethane (200 mL) and the solution was transferred to a500 mL separatory funnel. The solution was washed with water (100 mL)and the layers were separated. The brown aqueous layers was extractedwith dichloromethane (50 mL) and the dark brown dichloromethane extractscombined, washed with brine (100 mL), dried (MgSO₄), filtered and rotaryevaporated. This gave 30.49 g (74% pure by HPLC at 254 nm) of a crudeblack oil. The crude product was purified by silica gel chromatography(0 to 100% ethyl acetate/hexanes) to afford a beige solid (23.2 g, 89%):mp 79-81° C.; ¹H NMR (300 MHz, CDCl₃) δ 9.11 (d, J=1.7 Hz, 1H), 8.71 (d,J=4.8 Hz, 1H), 8.27-8.13 (m, 1H), 7.42 (dd, J=8.0, 4.9 Hz, 1H), 3.90(bs, 1H), 3.69 (bs, 1H), 2.80 (bs, 2H), 2.47 (bs, 1H), 2.02 (s, 3H),1.21 (q, J=7.3 Hz, 6H); ESIMS m/z 356 (M+1).

Example 74 Preparation of 3-(4-Chloro-thiazole-2-yl)pyridine

To a suspension of pyridin-3-ylboronic acid (3.87 g, 31.5 mmol) intoluene (120 mL) was added 2,4-dichlorothiazole (4.62 g, 30 mmol)followed by ethanol (60 mL) and a 2.0 M solution of K₂CO₃ (30.0 mL, 60.0mmol). The solution was degassed by applying vacuum and then purgingwith nitrogen (3 times). To the reaction mixture was addedtetrakis(triphenylphosphine)palladium (0) (1.733 g, 1.500 mmol) and theflask was heated at 95° C. under nitrogen for 16 hours. The aqueouslayer was removed and the organic layer was concentrated. The crudeproduct was purified via silica gel chromatography (0-100% ethylacetate/hexanes) to afford the title compound as a brown solid (4.6 g,74%): mp 84-86° C.; IR (KBr) 3092 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ9.16-9.13 (m, 1H), 8.69 (dd, J=4.8, 1.6 Hz, 1H), 8.23 (ddd, J=8.0, 2.2,1.7 Hz, 1H), 7.40 (ddd, J=8.0, 4.8, 0.8 Hz, 1H), 7.16 (s, 1H).

Example 75 Preparation of 2,2-dimethyl-3-(methylthio)propanoic acid

Example 75 can be prepared as demonstrated in the literature (referenceMusker, W. K.; et al. J. Org. Chem. 1996, 51, 1026-1029). Sodiummethanethiolate (1.0 g, 14 mmol, 2.0 equiv) was added to a stirredsolution of 3-chloro-2,2-dimethylpropanoic acid (1.0 g, 7.2 mmol, 1.0equiv) in N,N-dimethylformamide (3.7 mL) at 0° C. The resulting brownsuspension was allowed to warm to 23° C. and stirred for 24 h. Thereaction mixture was diluted with a saturated solution of sodiumbicarbonate (300 mL) and washed with diethyl ether (3×75 mL). Theaqueous layer was acidified to pH≈1 with concentrated hydrochloric acidand extracted with diethyl ether (3×75 mL). The combined organic layerswere dried (sodium sulfate), gravity filtered, and concentrated toafford a colorless oil (1.2 g, 99% crude yield). ¹H NMR (300 MHz, CDCl₃)δ 2.76 (s, 2H), 2.16 (s, 3H), 1.30 (s, 6H).

Example 76 Preparation of 3-methyl-3-methylsulfanyl-butyric acid

Example 76 was made using the procedures disclosed in J. Chem Soc Perkin1, 1992, 10, 1215-21).

Example 77 Preparation of 3-methylsulfanyl-butyric acid

Example 77 was made using the procedures disclosed in Synthetic Comm.,1985, 15 (7), 623-32.

Example 78 Preparation of tetrahydro-thiophene-3-carboxylic acid

Example 78 was made using the procedures disclosed in Heterocycles,2007, 74, 397-409.

Example 79 Preparation of 2-methyl-3-methylsulfanyl-butyric acid

Example 79 was made using the procedures disclosed in J. Chem Soc Perkin1, 1992, 10, 1215-21.

Example 80 Preparation of (1S,2S)-2-(methylthio)cyclopropanecarboxylicacid

Example 80 was made using the procedures disclosed in Synthetic Comm.,2003, 33 (5); 801-807.

The following compounds were made in accordance with Schemes I throughXXI above.

The following compounds were made in accordance with the proceduresshown in Scheme I steps a, b, e, i and j followed by Scheme VII above:138, 174.

The following compounds were made in accordance with the proceduresshown in Scheme I steps a, b, e, i and j above: 120.

Compound 476 was prepared according to Scheme XVIII.

Compound 502 was prepared from Compound 481 according to the Scheme IX(step c) and the Scheme V (Step a), respectively.

Compound 494 was prepared from Compound 481 according to Scheme IX (stepc) and Scheme VIII (step a), respectively.

Compound 503 was prepared from Compound 277 according to the Scheme VIII(steps b and c), Scheme IX (step a, c) and Scheme III (steps f) andScheme V (step a), respectively.

Compound 451 was prepared as disclosed in Scheme VII from compound 421.

Compound 459 was prepared as disclosed in Scheme VII from compound 451.

The following compound was made in accordance with the procedures shownin Scheme I steps c, e, and h followed by Scheme XIV steps a and b: 472.

The following compounds were made in accordance with the proceduresshown in Scheme I steps c, e, and h followed by Scheme XIV step a: 449,386, 398, 450, 511, 512.

The following compounds were made in accordance with the proceduresshown in Scheme I steps c, e, i, j, and k, Scheme XVI step a, and SchemeVIII step b then a, respectively: 583, 584, and 586.

The following compound was made in accordance with the procedures shownin Scheme I steps c, e, i, j, and k followed by Scheme XVI step a: 580.

The following compound was made in accordance with the procedures shownin Scheme I steps c, e, i, j, and k, Scheme XVI step a, and Scheme VIIIstep b, respectively: 581.

The following compound was made in accordance with the procedures shownin Scheme I steps c, e, i, j, and k, Scheme XVI step a, Scheme VIII stepb, and Scheme XIV step a, respectively: 585.

The following compound was made in accordance with the procedures shownin Scheme I steps c, e, i, j, and k, Scheme XVI step a, Scheme VIII stepb, and Scheme II step d, respectively: 587.

The following compound was made in accordance with the procedures shownin Scheme II steps a, b, c: 309.

Compounds 473, 500, 508, 509, 513, 515, 551 were made in accordance withSchemes III (step b, c) and Scheme IV.

Compounds 469, 470, 474, 475, 501, 510, 514, 558 were made in accordancewith Schemes III (step b, c), Scheme IV and Scheme VII.

Compounds 527, 528, 529, 540, 541, 542, 543, 544, 545, 547, 548, 550,554, 555, 556, 557, 561, 562, 563, 564, 570, 571, 574, 575, 576, 577,578, 579 were made in accordance with Schemes III (step b, c, d, e, f)and Scheme XVI.

Compound 549 was made in accordance with Schemes III (step b, c, d, e,J), Scheme XVI and Scheme VII (step a).

Compounds 139-142, 252 were made in accordance with Schemes I and V.

Compounds 143-148 were made in accordance with Schemes I, V, and VII.

Compounds 133-136 were made in accordance with Schemes II and V.

Compounds 251 and 265 were made in accordance with Scheme III.

Compound 296 was made in accordance with Schemes III and V.

Compound 317 was made in accordance with Schemes III and X.

Compound 318 was made in accordance with Schemes III and IX.

Compounds 149-151, 160, 241, 243-245, and 267 were made in accordancewith Scheme III.

Compounds 193, 209-210, 221-224, 226, 231, 233, 236, 237, 240, 253, 254,255, 262-264, 266, 274, 275, 278, 279, 298, 299, 305, 308, 525, 530-532,535, 539 and 546 were made in accordance with Schemes III and V.

Compounds 137, 153-155, 158-159, 161, 169-170, 172, 175, 176, 196, 197,204-205 and 207 were made in accordance with Schemes III and VIII.

Compounds 452 was made in accordance with Schemes III and IX.

Compounds 297, 352, 422 and 478 were made in accordance with Schemes IIIand X.

Compounds 186, 187, 194, 206, 208, 232, 268, 276, 280-283, 290-295,310-312, 326, 327, 329, 330-347, 350, 351, 355, 365, 533, 534, 536 and573 were made in accordance with Schemes III and XVI.

Compounds 152, 162, 173, 183-185, 188, 189, 195 and 200 were made inaccordance with Schemes III, IV and V.

Compounds 225, 229, 230, 234, 235, 238, 239, 246, 247, 249, 250,256-261, 269-273, 288, 289, 306, 307, 314, 315, 348, 349, 559 and 560were made in accordance with Schemes III, V and VII.

Compound 211 was made in accordance with Schemes III, V and VIII.

Compound 328 was made in accordance with Schemes III, IX and XVI.

Compounds 303, 366 and 423 were made in accordance with Schemes III(step a-c), Scheme X (step a-d) and Scheme II (step d).

Compound 364 was made in accordance with Schemes III (step a-c), SchemeX (step a-d) and Scheme VIII (step a and b).

Compounds 384, 385, 424, 425, 441 and 456 were made in accordance withSchemes III (step a-c), Scheme X (step a-d), Scheme II (step d and e)and Scheme V.

Compounds 354, 457, 458, 480, 498, 499 and 505 were made in accordancewith Schemes III (step a-e), Scheme IX (step a), Scheme III (step ft andScheme V.

Compounds 504, 506, 507 and 526 were made in accordance with Schemes III(step a-e), Scheme IX (step a), Scheme III (step f), Scheme V and SchemeVII.

Compounds 392, 393, 427, 454 and 455 were made in accordance withSchemes III (step a-c), Scheme X (step a-d), Scheme II (step d and e),Scheme V and Scheme VII.

Compound 477 and 496 were made in accordance with Schemes III (stepa-e), Scheme V.

Compounds 356, 426, and 460-468 were prepared according to Scheme II(steps c-e) and Scheme XVI.

Compounds 357, 518, 567 and 568 were prepared according to Scheme II(steps c and d).

Compounds 358-362, 367-374, 381, 382, 383, 387-390, 394, 396, 397,420-421 and 428-440 were prepared according to Scheme XVI.

Compounds 167 and 168 were prepared in accordance with Schemes III, Vand XI.

Compound 165 was made according to Scheme III.

Compounds 166, 190, 300 and 446-448 were prepared in accordance withSchemes III and V.

Compounds 178, 179, 181, 182, 191, 192, 198 and 199 were prepared inaccordance with Schemes III and VI.

Compounds 212-220, 248, 319, 324, 405, 409, 411, 413, 401, 415, 442-445,487, 516, 517, 538, 552, 553, 566, 569, 588 were prepared in accordancewith Schemes III and XVI.

Compounds 284, 301, 302, 375-378, 379, 380, 482-486, 491-493 wereprepared according to Scheme II.

Compounds 285, 287 520-524, 537, 565 were prepared in accordance withSchemes III, XVI and VII.

Compound 286 was prepared according to Schemes II and V.

Compounds 320-323, 400, 402-404, 407, 410 and 412 were prepared inaccordance with Schemes II and XVI.

Compound 395 was prepared in accordance with Schemes XII and XVI.

Compounds 399, 406, 408, 414, 416-418 were prepared in accordance withSchemes II, III and XVI.

Compound 489 was prepared in accordance with Schemes III, XVI and VIII.

Compounds 201 and 202 were prepared in accordance with Scheme II.

Compound 177 was prepared in accordance with Schemes III and VI.

Compound 325 was prepared in accordance with Schemes II and VI.

Compound 488 was prepared in accordance with Schemes III and XVI.

Compound 490 was prepared in accordance with Schemes III, XVI, and VIII.

Insecticidal Testing

The compounds were tested against cotton aphid, green peach aphid, andsweet potato whitefly using procedures described in the followingexamples and reported in Table 2.

In each case of Table 2, the rating scale is as follows at 200 ppm.

% Control (or Mortality) Rating 80-100 A Less than 80 B Not tested C

Example 81 Insecticidal Test for Green Peach Aphid (Myzus persicae) inFoliar Spray Assay

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 green peach aphids (wingless adult and nymph) one day prior tochemical application. Four pots with individual seedlings were used foreach treatment. Compounds (2 mg) were dissolved in 2 mL ofacetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm. Thestock solutions were diluted 5× with 0.025% Tween 20 in H₂O to obtain atest solution at 200 ppm. A hand-held Devilbiss sprayer was used forspraying a solution to both sides of cabbage leaves until runoff.Reference plants (solvent check) were sprayed with the diluent only.Treated plants were held in a holding room for three days atapproximately 25° C. and 40% relative humidity (RH) prior to grading.Evaluation was conducted by counting the number of live aphids per plantunder a microscope. Insecticidal activity was measured by using Abbott'scorrection formula are presented in Table 2: (See col. “MYZUPE”).Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live aphids on solvent check plants    -   Y=No. of live aphids on treated plants

Example 82 Insecticidal Test for Cotton Aphid (Aphis gossypii) in FoliarSpray Assay

Squash or cotton seedlings with fully expanded cotyledon leaves weretrimmed to one cotyledon per plant and infested with cotton aphid(wingless adult and nymph) one day prior to chemical application. Eachplant was examined before chemical application to ensure uniforminfestation (ca. 30-70 aphids per plant). Compounds (2 mg) weredissolved in 2 mL of acetone/methanol (1:1) solvent, forming stocksolutions of 1000 ppm. The stock solutions were diluted 5× with 0.025%Tween 20 in H₂O to obtain a solution at 200 ppm. A hand-held Devilbissaspirator type sprayer was used to apply the spray solutions untilrunoff to both sides of the squash cotyledon leaves. Four plants (4replications) were used for each concentration of each compound.Reference plants (solvent check) were sprayed with the diluent only.Treated plants were held in a holding room for three days atapproximately 25° C. and 40% RH before the number of live aphids on eachplant was recorded. Insecticidal activity was measured by Corrected %Control using Abbott's correction formula and presented in Table 2 (seecol. “APHIGO”):Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live aphids on solvent check plants    -   Y=No. of live aphids on treated plants

Example 83 Insecticidal Test for Sweet Potato Whitefly-Crawler (Bemisiatabaci) in Foliar Spray Assay

Cotton plants grown in 3-inch pots, with 1 small (3-5 cm) true leaf,were used as test substrate. The plants were placed in a room withwhitefly adults. Adults were allowed to deposit eggs for 2-3 days. Aftera 2-3 day egg-laying period, plants were taken from the adult whiteflyroom. Adults were blown off leaves using a hand-held Devilbiss sprayer(23 psi). Plants with egg infestation (100-300 eggs per plant) wereplaced in a holding room for 5-6 days at 82° F. and 50% RH for egg hatchand crawler stage to develop. Four cotton plants were used for eachtreatment. Compounds (2 mg) were dissolved in 1 mL of acetone solvent,forming stock solutions of 2000 ppm. The stock solutions were diluted10× with 0.025% Tween 20 in H₂O to obtain a test solution at 200 ppm. Ahand-held Devilbiss sprayer was used for spraying a solution to bothsides of cotton leaf until runoff. Reference plants (solvent check) weresprayed with the diluent only. Treated plants were held in a holdingroom for 8-9 days at approximately 82° F. and 50% RH prior to grading.Evaluation was conducted by counting the number of live nymphs per plantunder a microscope. Insecticidal activity was measured by using Abbott'scorrection formula and presented in Table 2 (see col. “BEMITA”):Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live nymphs on solvent check plants    -   Y=No. of live nymphs on treated plants        Pesticidally Acceptable Acid Addition Salts, Salt Derivatives,        Solvates, Ester Derivatives, Polymorphs, Isotopes and        Radionuclides

Molecules of Formula I may be formulated into pesticidally acceptableacid addition salts. By way of a non-limiting example, an amine functioncan form salts with hydrochloric, hydrobromic, sulfuric, phosphoric,acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic,succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic,benzenesulfonic, methanesulfonic, ethanesulfonic,hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally,by way of a non-limiting example, an acid function can form saltsincluding those derived from alkali or alkaline earth metals and thosederived from ammonia and amines. Examples of preferred cations includesodium, potassium, magnesium, and ammonium cations.

Molecules of Formula I may be formulated into salt derivatives. By wayof a non-limiting example, a salt derivative can be prepared bycontacting a free base with a sufficient amount of the desired acid toproduce a salt. A free base may be regenerated by treating the salt witha suitable dilute aqueous base solution such as dilute aqueous sodiumhydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate.As an example, in many cases, a pesticide, such as 2,4-D, is made morewater-soluble by converting it to its dimethylamine salt.

Molecules of Formula I may be formulated into stable complexes with asolvent, such that the complex remains intact after the non-complexedsolvent is removed. These complexes are often referred to as “solvates.”However, it is particularly desirable to form stable hydrates with wateras the solvent.

Molecules of Formula I may be made as various crystal polymorphs.Polymorphism is important in the development of agrochemicals sincedifferent crystal polymorphs or structures of the same molecule can havevastly different physical properties and biological performances.

Molecules of Formula I may be made with different isotopes. Ofparticular importance are molecules having ²H (also known as deuterium)in place of ¹H.

Molecules of Formula I may be made with different radionuclides. Ofparticular importance are molecules having ¹⁴C.

Stereoisomers

Molecules of Formula I may exist as one or more stereoisomers. Thus,certain molecules can be produced as racemic mixtures. It will beappreciated by those skilled in the art that one stereoisomer may bemore active than the other stereoisomers. Individual stereoisomers maybe obtained by known selective synthetic procedures, by conventionalsynthetic procedures using resolved starting materials, or byconventional resolution procedures.

Insecticides

Molecules of Formula I may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withone or more of the following insecticides—1,2-dichloropropane,abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin,acrylonitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin,allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone,alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate,amitraz, anabasine, athidathion, azadirachtin, azamethiphos,azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate,barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin,beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin,biopermethrin, bistrifluoron, borax, boric acid, bromfenvinfos,bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb,buprofezin, butacarb, butathiofos, butocarboxim, butonate,butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide,camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbontetrachloride, carbophenothion, carbosulfan, cartap, cartaphydrochloride, chlorantraniliprole, chlorbicyclen, chlordane,chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos,chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform,chloropicrin, chlorphoxim, chlorprazophos, chlorpyrifos,chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerinII, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copperacetoarsenite, copper arsenate, copper naphthenate, copper oleate,coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite,cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclethrin,cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin,cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion,demephion-O, demephion-S, demeton, demeton-methyl, demeton-O,demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon,diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon,dichlofenthion, dichlorvos, dicresyl, dicrotophos, dicyclanil, dieldrin,diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate,dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop,dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion,disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium,DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin,emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin,EPN, epofenonane, eprinomectin, esdepallethrine, esfenvalerate, etaphos,ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethylformate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethyleneoxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor,fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb,fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion,fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid,flubendiamide (additionally resolved isomers thereof), flucofuron,flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufenprox,fluvalinate, fonofos, formetanate, formetanate hydrochloride,formothion, formparanate, formparanate hydrochloride, fosmethilan,fospirate, fosthietan, fufenozide, furathiocarb, furethrin,gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD,heptachlor, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon,hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin,indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos,isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane,isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos,juvenile hormone I, juvenile hormone II, juvenile hormone III, kelevan,kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos,lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben,mazidox, mecarbam, mecarphon, menazon, meperfluthrin, mephosfolan,mercurous chloride, mesulfenfos, metaflumizone, methacrifos,methamidophos, methidathion, methiocarb, methocrotophos, methomyl,methoprene, methothrin, methoxychlor, methoxyfenozide, methyl bromide,methyl isothiocyanate, methylchloroform, methylene chloride,metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate,milbemectin, milbemycin oxime, mipafox, mirex, molosultap,monocrotophos, monomehypo, monosultap, morphothion, moxidectin,naftalofos, naled, naphthalene, nicotine, nifluridide, nitenpyram,nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl,oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene,parathion, parathion-methyl, penfluoron, pentachlorophenol, permethrin,phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan,phosmet, phosnichlor, phosphamidon, phosphine, phoxim, phoxim-methyl,pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassiumarsenite, potassium thiocyanate, pp′-DDT, prallethrin, precocene I,precocene II, precocene III, primidophos, profenofos, profluralin,profluthrin, promacyl, promecarb, propaphos, propetamphos, propoxur,prothidathion, prothiofos, prothoate, protrifenbute, pymetrozine,pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrin I,pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion,pyrifluquinazon, pyrimidifen, pyrimitate, pyriprole, pyriproxyfen,quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide,resmethrin, rotenone, ryania, sabadilla, schradan, selamectin,silafluofen, silica gel, sodium arsenite, sodium fluoride, sodiumhexafluorosilicate, sodium thiocyanate, sophamide, spinetoram, spinosad,spiromesifen, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid,sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tau-fluvalinate,tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron,tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachloroethane,tetrachlorvinphos, tetramethrin, tetramethylfluthrin,theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime,thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon,thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin,tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene,triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat,trifenofos, triflumuron, trimethacarb, triprene, vamidothion,vaniliprole, XMC, xylylcarb, zeta-cypermethrin, zolaprofos (collectivelythese commonly named insecticides are defined as the “InsecticideGroup”).

Acaricides

Molecules of Formula I may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withone or more of the following acaricides—acequinocyl, amidoflumet,arsenous oxide, azobenzene, azocyclotin, benomyl, benoxafos,benzoximate, benzyl benzoate, bifenazate, binapacryl, bromopropylate,chinomethionat, chlorbenside, chlorfenethol, chlorfenson,chlorfensulphide, chlorobenzilate, chloromebuform, chloromethiuron,chloropropylate, clofentezine, cyenopyrafen, cyflumetofen, cyhexatin,dichlofluanid, dicofol, dienochlor, diflovidazin, dinobuton, dinocap,dinocap-4, dinocap-6, dinocton, dinopenton, dinosulfon, dinoterbon,diphenyl sulfone, disulfuram, dofenapyn, etoxazole, fenazaquin,fenbutatin oxide, fenothiocarb, fenpyroximate, fenson, fentrifanil,fluacrypyrim, fluazuron, flubenzimine, fluenetil, flumethrin,fluorbenside, hexythiazox, mesulfen, MNAF, nikkomycins, proclonol,propargite, quintiofos, spirodiclofen, sulfuram, sulfur, tetradifon,tetranactin, tetrasul, and thioquinox (collectively these commonly namedacaricides are defined as the “Acaricide Group”).

Nematicides

Molecules of Formula I may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withone or more of the following nematicides—1,3-dichloropropene,benclothiaz, dazomet, dazomet-sodium, DBCP, DCIP, diamidafos,fluensulfone, fosthiazate, furfural, imicyafos, isamidofos, isazofos,metam, metam-ammonium, metam-potassium, metam-sodium, phosphocarb, andthionazin (collectively these commonly named nematicides are defined asthe “Nematicide Group”)

Fungicides

Molecules of Formula I may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withone or more of the following fungicides—(3-ethoxypropyl)mercury bromide,2-methoxyethylmercury chloride, 2-phenylphenol, 8-hydroxyquinolinesulfate, 8-phenylmercurioxyquinoline, acibenzolar, acibenzolar-S-methyl,acypetacs, acypetacs-copper, acypetacs-zinc, aldimorph, allyl alcohol,ametoctradin, amisulbrom, ampropylfos, anilazine, aureofungin,azaconazole, azithiram, azoxystrobin, barium polysulfide, benalaxyl,benalaxyl-M, benodanil, benomyl, benquinox, bentaluron, benthiavalicarb,benthiavalicarb-isopropyl, benzalkonium chloride, benzamacril,benzamacril-isobutyl, benzamorf, benzohydroxamic acid, bethoxazin,binapacryl, biphenyl, bitertanol, bithionol, bixafen, blasticidin-S,Bordeaux mixture, boscalid, bromuconazole, bupirimate, Burgundy mixture,buthiobate, butylamine, calcium polysulfide, captafol, captan,carbamorph, carbendazim, carboxin, carpropamid, carvone, Cheshuntmixture, chinomethionat, chlobenthiazone, chloraniformethan, chloranil,chlorfenazole, chlorodinitronaphthalene, chloroneb, chloropicrin,chlorothalonil, chlorquinox, chlozolinate, climbazole, clotrimazole,copper acetate, copper carbonate, basic, copper hydroxide, coppernaphthenate, copper oleate, copper oxychloride, copper silicate, coppersulfate, copper zinc chromate, cresol, cufraneb, cuprobam, cuprousoxide, cyazofamid, cyclafuramid, cycloheximide, cyflufenamid, cymoxanil,cypendazole, cyproconazole, cyprodinil, dazomet, dazomet-sodium, DBCP,debacarb, decafentin, dehydroacetic acid, dichlofluanid, dichlone,dichlorophen, dichlozoline, diclobutrazol, diclocymet, diclomezine,diclomezine-sodium, dicloran, diethofencarb, diethyl pyrocarbonate,difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin,diniconazole, diniconazole-M, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine,dipyrithione, disulfuram, ditalimfos, dithianon, DNOC, DNOC-ammonium,DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorphbenzoate, dodicin, dodicin-sodium, dodine, drazoxolon, edifenphos,epoxiconazole, etaconazole, etem, ethaboxam, ethirimol, ethoxyquin,ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate,ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate,etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenarimol,fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil,fenpropidin, fenpropimorph, fentin, fentin chloride, fentin hydroxide,ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph,fluopicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin,fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil,flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl,fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, furcarbanil,furconazole, furconazole-cis, furfural, furmecyclox, furophanate,glyodin, griseofulvin, guazatine, halacrinate, hexachlorobenzene,hexachlorobutadiene, hexaconazole, hexylthiofos, hydrargaphen,hymexazol, imazalil, imazalil nitrate, imazalil sulfate, imibenconazole,iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate,iodomethane, ipconazole, iprobenfos, iprodione, iprovalicarb,isoprothiolane, isopyrazam, isotianil, isovaledione, kasugamycin,kresoxim-methyl, mancopper, mancozeb, mandipropamid, maneb, mebenil,mecarbinzid, mepanipyrim, mepronil, meptyldinocap, mercuric chloride,mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam,metam-ammonium, metam-potassium, metam-sodium, metazoxolon, metconazole,methasulfocarb, methfuroxam, methyl bromide, methyl isothiocyanate,methylmercury benzoate, methylmercury dicyandiamide, methylmercurypentachlorophenoxide, metiram, metominostrobin, metrafenone,metsulfovax, milneb, myclobutanil, myclozolin,N-(ethylmercury)-p-toluenesulphonanilide, nabam, natamycin,nitrostyrene, nitrothal-isopropyl, nuarimol, OCH, octhilinone, ofurace,orysastrobin, oxadixyl, oxine-copper, oxpoconazole, oxpoconazolefumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen,pentachlorophenol, penthiopyrad, phenylmercuriurea, phenylmercuryacetate, phenylmercury chloride, phenylmercury derivative ofpyrocatechol, phenylmercury nitrate, phenylmercury salicylate,phosdiphen, phthalide, picoxystrobin, piperalin, polycarbamate,polyoxins, polyoxorim, polyoxorim-zinc, potassium azide, potassiumpolysulfide, potassium thiocyanate, probenazole, prochloraz,procymidone, propamocarb, propamocarb hydrochloride, propiconazole,propineb, proquinazid, prothiocarb, prothiocarb hydrochloride,prothioconazole, pyracarbolid, pyraclostrobin, pyraclostrobin,pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril,pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor,pyroxyfur, quinacetol, quinacetol sulfate, quinazamid, quinconazole,quinoxyfen, quintozene, rabenzazole, salicylanilide, sedaxane,silthiofam, simeconazole, sodium azide, sodium orthophenylphenoxide,sodium pentachlorophenoxide, sodium polysulfide, spiroxamine,streptomycin, sulfur, sultropen, TCMTB, tebuconazole, tebufloquin,tecloftalam, tecnazene, tecoram, tetraconazole, thiabendazole,thiadifluor, thicyofen, thifluzamide, thiochlorfenphim, thiomersal,thiophanate, thiophanate-methyl, thioquinox, thiram, tiadinil, tioxymid,tolclofos-methyl, tolylfluanid, tolylmercury acetate, triadimefon,triadimenol, triamiphos, triarimol, triazbutil, triazoxide, tributyltinoxide, trichlamide, tricyclazole, tridemorph, trifloxystrobin,triflumizole, triforine, triticonazole, uniconazole, uniconazole-P,validamycin, valifenalate, vinclozolin, zarilamid, zinc naphthenate,zineb, ziram, zoxamide (collectively these commonly named fungicides aredefined as the “Fungicide Group”).

Herbicides

Molecules of Formula I may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withone or more of the following herbicides—2,3,6-TBA,2,3,6-TBA-dimethylammonium, 2,3,6-TBA-sodium, 2,4,5-T,2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl,2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl, 2,4,5-T-butyl,2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl,2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium,2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl,2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl,2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium,2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium,2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB,2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl,2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium,2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium,2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium,2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium,2,4-D-trolamine, 3,4-DA, 3,4-DB, 3,4-DP, 4-CPA, 4-CPB, 4-CPP,acetochlor, acifluorfen, acifluorfen-methyl, acifluorfen-sodium,aclonifen, acrolein, alachlor, allidochlor, alloxydim, alloxydim-sodium,allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone,amidosulfuron, aminocyclopyrachlor, aminocyclopyrachlor-methyl,aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium,aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl, amitrole,ammonium sulfamate, anilofos, anisuron, asulam, asulam-potassium,asulam-sodium, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne,barban, BCPC, beflubutamid, benazolin, benazolin-dimethylammonium,benazolin-ethyl, benazolin-potassium, bencarbazone, benfluralin,benfuresate, bensulfuron, bensulfuron-methyl, bensulide, bentazone,bentazone-sodium, benzadox, benzadox-ammonium, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzoylprop, benzoylprop-ethyl,benzthiazuron, bicyclopyrone, bifenox, bilanafos, bilanafos-sodium,bispyribac, bispyribac-sodium, borax, bromacil, bromacil-lithium,bromacil-sodium, bromobonil, bromobutide, bromofenoxim, bromoxynil,bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate,bromoxynil-potassium, brompyrazon, butachlor, butafenacil, butamifos,butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon,butylate, cacodylic acid, cafenstrole, calcium chlorate, calciumcyanamide, cambendichlor, carbasulam, carbetamide, carboxazole,carfentrazone, carfentrazone-ethyl, CDEA, CEPC, chlomethoxyfen,chloramben, chloramben-ammonium, chloramben-diolamine,chloramben-methyl, chloramben-methylammonium, chloramben-sodium,chloranocryl, chlorazifop, chlorazifop-propargyl, chlorazine,chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenac-sodium,chlorfenprop, chlorfenprop-methyl, chlorflurazole, chlorflurenol,chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl,chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil,chlorprocarb, chlorpropham, chlorsulfuron, chlorthal,chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, cinidon-ethyl,cinmethylin, cinosulfuron, cisanilide, clethodim, cliodinate,clodinafop, clodinafop-propargyl, clofop, clofop-isobutyl, clomazone,clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,clopyralid-olamine, clopyralid-potassium,clopyralid-tris(2-hydroxypropyl)ammonium, cloransulam,cloransulam-methyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol,cumyluron, cyanamide, cyanatryn, cyanazine, cycloate, cyclosulfamuron,cycloxydim, cycluron, cyhalofop, cyhalofop-butyl, cyperquat, cyperquatchloride, cyprazine, cyprazole, cypromid, daimuron, dalapon,dalapon-calcium, dalapon-magnesium, dalapon-sodium, dazomet,dazomet-sodium, delachlor, desmedipham, desmetryn, di-allate, dicamba,dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium,dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium,dicamba-trolamine, dichlobenil, dichloralurea, dichlormate, dichlorprop,dichlorprop-2-ethylhexyl, dichlorprop-butotyl,dichlorprop-dimethylammonium, dichlorprop-ethylammonium,dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,dichlorprop-P-dimethylammonium, dichlorprop-potassium,dichlorprop-sodium, diclofop, diclofop-methyl, diclosulam, diethamquat,diethamquat dichloride, diethatyl, diethatyl-ethyl, difenopenten,difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate,diflufenican, diflufenzopyr, diflufenzopyr-sodium, dimefuron,dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P,dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam,dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine,dinoseb-sodium, dinoseb-trolamine, dinoterb, dinoterb acetate,diphacinone-sodium, diphenamid, dipropetryn, diquat, diquat dibromide,disul, disul-sodium, dithiopyr, diuron, DMPA, DNOC, DNOC-ammonium,DNOC-potassium, DNOC-sodium, DSMA, EBEP, eglinazine, eglinazine-ethyl,endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium,epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron,ethametsulfuron-methyl, ethidimuron, ethiolate, ethofumesate, ethoxyfen,ethoxyfen-ethyl, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD,fenasulam, fenoprop, fenoprop-3-butoxypropyl, fenoprop-butomethyl,fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl,fenoprop-potassium, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P,fenoxaprop-P-ethyl, fenoxasulfone, fenteracol, fenthiaprop,fenthiaprop-ethyl, fentrazamide, fenuron, fenuron TCA, ferrous sulfate,flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl,flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, florasulam,fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P,fluazifop-P-butyl, fluazolate, flucarbazone, flucarbazone-sodium,flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr,flufenpyr-ethyl, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl,flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen,fluoroglycofen-ethyl, fluoromidine, fluoronitrofen, fluothiuron,flupoxam, flupropacil, flupropanate, flupropanate-sodium,flupyrsulfuron, flupyrsulfuron-methyl-sodium, fluridone,fluorochloridone, fluoroxypyr, fluoroxypyr-butomethyl,fluoroxypyr-meptyl, flurtamone, fluthiacet, fluthiacet-methyl,fomesafen, fomesafen-sodium, foramsulfuron, fosamine, fosamine-ammonium,furyloxyfen, glufosinate, glufosinate-ammonium, glufosinate-P,glufosinate-P-ammonium, glufosinate-P-sodium, glyphosate,glyphosate-diammonium, glyphosate-dimethylammonium,glyphosate-isopropylammonium, glyphosate-monoammonium,glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium,halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop,haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl,haloxyfop-P-methyl, haloxyfop-sodium, hexachloroacetone, hexaflurate,hexazinone, imazamethabenz, imazamethabenz-methyl, imazamox,imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr,imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium,imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium,imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane,iodosulfuron, iodosulfuron-methyl-sodium, ioxynil, ioxynil octanoate,ioxynil-lithium, ioxynil-sodium, ipazine, ipfencarbazone, iprymidam,isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin,isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole,isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron,MAA, MAMA, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl,MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl,MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium,MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl,MCPB-methyl, MCPB-sodium, mecoprop, mecoprop-2-ethylhexyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-isoctyl, mecoprop-methyl, mecoprop-P,mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium,mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medinoterb,medinoterb acetate, mefenacet, mefluidide, mefluidide-diolamine,mefluidide-potassium, mesoprazine, mesosulfuron, mesosulfuron-methyl,mesotrione, metam, metam-ammonium, metamifop, metamitron,metam-potassium, metam-sodium, metazachlor, metazosulfuron, metflurazon,methabenzthiazuron, methalpropalin, methazole, methiobencarb,methiozolin, methiuron, methometon, methoprotryne, methyl bromide,methyl isothiocyanate, methyldymron, metobenzuron, metolachlor,metosulam, metoxuron, metribuzin, metsulfuron, metsulfuron-methyl,molinate, monalide, monisouron, monochloroacetic acid, monolinuron,monuron, monuron TCA, morfamquat, morfamquat dichloride, MSMA,naproanilide, napropamide, naptalam, naptalam-sodium, neburon,nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen,norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene,orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon,oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone,oxyfluorfen, parafluoron, paraquat, paraquat dichloride, paraquatdimetilsulfate, pebulate, pelargonic acid, pendimethalin, penoxsulam,pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid,phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron,phenylmercury acetate, picloram, picloram-2-ethylhexyl,picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium,picloram-triethylammonium, picloram-tris(2-hydroxypropyl)ammonium,picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide,potassium cyanate, pretilachlor, primisulfuron, primisulfuron-methyl,procyazine, prodiamine, profluazol, profluralin, profoxydim,proglinazine, proglinazine-ethyl, prometon, prometryn, propachlor,propanil, propaquizafop, propazine, propham, propisochlor,propoxycarbazone, propoxycarbazone-sodium, propyrisulfuron, propyzamide,prosulfalin, prosulfocarb, prosulfuron, proxan, proxan-sodium,prynachlor, pydanon, pyraclonil, pyraflufen, pyraflufen-ethyl,pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazosulfuron-ethyl,pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate,pyriftalid, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrithiobac,pyrithiobac-sodium, pyroxasulfone, pyroxsulam, quinclorac, quinmerac,quinoclamine, quinonamid, quizalofop, quizalofop-ethyl, quizalofop-P,quizalofop-P-ethyl, quizalofop-P-tefuryl, rhodethanil, rimsulfuron,saflufenacil, sebuthylazine, secbumeton, sethoxydim, siduron, simazine,simeton, simetryn, SMA, S-metolachlor, sodium arsenite, sodium azide,sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron,sulfometuron-methyl, sulfosulfuron, sulfuric acid, sulglycapin, swep,TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium,tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim,terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn,tetrafluoron, thenylchlor, thiazafluoron, thiazopyr, thidiazimin,thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron,thifensulfuron-methyl, thiobencarb, tiocarbazil, tioclorim, topramezone,tralkoxydim, tri-allate, triasulfuron, triaziflam, tribenuron,tribenuron-methyl, tricamba, triclopyr, triclopyr-butotyl,triclopyr-ethyl, triclopyr-triethylammonium, tridiphane, trietazine,trifloxysulfuron, trifloxysulfuron-sodium, trifluralin, triflusulfuron,triflusulfuron-methyl, trifop, trifop-methyl, trifopsime,trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron,vernolate, xylachlor, (collectively these commonly named herbicides aredefined as the “Herbicide Group”).

Biopesticides

Molecules of Formula I may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more biopesticides. The term “biopesticide” is used for microbialbiological pest control agents that are applied in a similar manner tochemical pesticides. Commonly these are bacterial, but there are alsoexamples of fungal control agents, including Trichoderma spp. andAmpelomyces quisqualis (a control agent for grape powdery mildew).Bacillus subtilis are used to control plant pathogens. Weeds and rodentshave also been controlled with microbial agents. One well-knowninsecticide example is Bacillus thuringiensis, a bacterial disease ofLepidoptera, Coleoptera, and Diptera. Because it has little effect onother organisms, it is considered more environmentally friendly thansynthetic pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi (e.g. Metarhizium anisopliae);

2. entomopathogenic nematodes (e.g. Steinernema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are notlimited to, baculoviruses, bacteria and other prokaryotic organisms,fungi, protozoa and Microsproridia. Biologically derived insecticidesinclude, but not limited to, rotenone, veratridine, as well as microbialtoxins; insect tolerant or resistant plant varieties; and organismsmodified by recombinant DNA technology to either produce insecticides orto convey an insect resistant property to the genetically modifiedorganism. In one embodiment, the molecules of Formula I may be used withone or more biopesticides in the area of seed treatments and soilamendments. The Manual of Biocontrol Agents gives a review of theavailable biological insecticide (and other biology-based control)products. Copping L. G. (ed.) (2004). The Manual of Biocontrol Agents(formerly the Biopesticide Manual) 3rd Edition. British Crop ProductionCouncil (BCPC), Farnham, Surrey UK.

Other Active Compounds

Molecules of Formula I may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more of the following:

-   1.    3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;-   2.    3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;-   3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;-   4.    4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;-   5.    3-chloro-N2-[1S)-1-methyl-2-(methylsulfonyl)ethyl]-N-1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide;-   6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;-   7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;-   8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;-   9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;-   10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzene sulfonamide;-   11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;-   12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;-   13.    3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide;-   14.    N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazone;-   15.    N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)    hydrazone nicotine;-   16.    O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-methyl    thiocarbonate;-   17.    (E)-N-1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N-1-methylacetamidine;-   18.    1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol;-   19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl    mesylate; and-   20.    N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.

Molecules of Formula I may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more compounds in the following groups: algicides, antifeedants,avicides, bactericides, bird repellents, chemosterilants, herbicidesafeners, insect attractants, insect repellents, mammal repellents,mating disrupters, molluscicides, plant activators, plant growthregulators, rodenticides, and/or virucides (collectively these commonlynamed groups are defined as the “AI Group”). It should be noted thatcompounds falling within the AI Group, Insecticide Group, FungicideGroup, Herbicide Group, Acaricide Group, or Nematicide Group might be inmore than one group, because of multiple activities the compound has.For more information consult the “COMPENDIUM OF PESTICIDE COMMON NAMES”located at http://www.alanwood.net/pesticides/in ex.html. Also consult“THE PESTICIDE MANUAL” 14th Edition, edited by C D S Tomlin, copyright2006 by British Crop Production Council, or its prior or more recenteditions.

Synergistic Mixtures and Synergists

Molecules of Formula I may be used with the compounds in the InsecticideGroup to form synergistic mixtures where the mode of action of suchcompounds compared to the mode of action of the molecules of Formula Iare the same, similar, or different. Examples of modes of actioninclude, but are not limited to: acetylcholinesterase inhibitor; sodiumchannel modulator; chitin biosynthesis inhibitor; GABA-gated chloridechannel antagonist; GABA and glutamate-gated chloride channel agonist;acetylcholine receptor agonist; MET I inhibitor; Mg-stimulated ATPaseinhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter;oxidative phosphorylation disrupter, and ryanodine receptor (RyRs).Additionally, molecules of Formula I may be used with compounds in theFungicide Group, Acaricide Group, Herbicide Group, or Nematicide Groupto form synergistic mixtures. Furthermore, molecules of Formula I may beused with other active compounds, such as the compounds under theheading “OTHER ACTIVE COMPOUNDS”, algicides, avicides, bactericides,molluscicides, rodenticides, virucides, herbicide safeners, adjuvants,and/or surfactants to form synergistic mixtures. Generally, weightratios of the molecules of Formula I in a synergistic mixture withanother compound are from about 10:1 to about 1:10, preferably fromabout 5:1 to about 1:5, and more preferably from about 3:1, and evenmore preferably about 1:1. Additionally, the following compounds areknown as synergists and may be used with the molecules disclosed inFormula I: piperonyl butoxide, piprotal, propyl isome, sesamex,sesamolin, sulfoxide, and tribufos (collectively these synergists aredefined as the “Synergists Group”).

Formulations

A pesticide is rarely suitable for application in its pure form. It isusually necessary to add other substances so that the pesticide can beused at the required concentration and in an appropriate form,permitting ease of application, handling, transportation, storage, andmaximum pesticide activity. Thus, pesticides are formulated into, forexample, baits, concentrated emulsions, dusts, emulsifiableconcentrates, fumigants, gels, granules, microencapsulations, seedtreatments, suspension concentrates, suspoemulsions, tablets, watersoluble liquids, water dispersible granules or dry flowables, wettablepowders, and ultra low volume solutions. For further information onformulation types see “Catalogue of Pesticide Formulation Types andInternational Coding System” Technical Monograph no 2, 5th Edition byCropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsionsprepared from concentrated formulations of such pesticides. Suchwater-soluble, water-suspendable, or emulsifiable formulations areeither solids, usually known as wettable powders, or water dispersiblegranules, or liquids usually known as emulsifiable concentrates, oraqueous suspensions. Wettable powders, which may be compacted to formwater dispersible granules, comprise an intimate mixture of thepesticide, a carrier, and surfactants. The concentration of thepesticide is usually from about 10% to about 90% by weight. The carrieris usually chosen from among the attapulgite clays, the montmorilloniteclays, the diatomaceous earths, or the purified silicates. Effectivesurfactants, comprising from about 0.5% to about 10% of the wettablepowder, are found among sulfonated lignins, condensednaphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates,alkyl sulfates, and non-ionic surfactants such as ethylene oxide adductsof alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenientconcentration of a pesticide, such as from about 50 to about 500 gramsper liter of liquid dissolved in a carrier that is either a watermiscible solvent or a mixture of water-immiscible organic solvent andemulsifiers. Useful organic solvents include aromatics, especiallyxylenes and petroleum fractions, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as the terpenicsolvents including rosin derivatives, aliphatic ketones such ascyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitableemulsifiers for emulsifiable concentrates are chosen from conventionalanionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticidesdispersed in an aqueous carrier at a concentration in the range fromabout 5% to about 50% by weight. Suspensions are prepared by finelygrinding the pesticide and vigorously mixing it into a carrier comprisedof water and surfactants. Ingredients, such as inorganic salts andsynthetic or natural gums may also be added, to increase the density andviscosity of the aqueous carrier. It is often most effective to grindand mix the pesticide at the same time by preparing the aqueous mixtureand homogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

Pesticides may also be applied as granular compositions that areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the pesticide,dispersed in a carrier that comprises clay or a similar substance. Suchcompositions are usually prepared by dissolving the pesticide in asuitable solvent and applying it to a granular carrier which has beenpre-formed to the appropriate particle size, in the range of from about0.5 to about 3 mm. Such compositions may also be formulated by making adough or paste of the carrier and compound and crushing and drying toobtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing thepesticide in powdered form with a suitable dusty agricultural carrier,such as kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from about 1% to about 10% of the pesticide. They canbe applied as a seed dressing or as a foliage application with a dustblower machine.

It is equally practical to apply a pesticide in the form of a solutionin an appropriate organic solvent, usually petroleum oil, such as thespray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. Insuch compositions the pesticide is dissolved or dispersed in a carrier,which is a pressure-generating propellant mixture. The aerosolcomposition is packaged in a container from which the mixture isdispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or anattractant or both. When the pests eat the bait they also consume thepesticide. Baits may take the form of granules, gels, flowable powders,liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure andhence can exist as a gas in sufficient concentrations to kill pests insoil or enclosed spaces. The toxicity of the fumigant is proportional toits concentration and the exposure time. They are characterized by agood capacity for diffusion and act by penetrating the pest'srespiratory system or being absorbed through the pest's cuticle.Fumigants are applied to control stored product pests under gas proofsheets, in gas sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending the pesticideparticles or droplets in plastic polymers of various types. By alteringthe chemistry of the polymer or by changing factors in the processing,microcapsules can be formed of various sizes, solubility, wallthicknesses, and degrees of penetrability. These factors govern thespeed with which the active ingredient within is released, which inturn, affects the residual performance, speed of action, and odor of theproduct.

Oil solution concentrates are made by dissolving pesticide in a solventthat will hold the pesticide in solution. Oil solutions of a pesticideusually provide faster knockdown and kill of pests than otherformulations due to the solvents themselves having pesticidal action andthe dissolution of the waxy covering of the integument increasing thespeed of uptake of the pesticide. Other advantages of oil solutionsinclude better storage stability, better penetration of crevices, andbetter adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsioncomprises oily globules which are each provided with a lamellar liquidcrystal coating and are dispersed in an aqueous phase, wherein each oilyglobule comprises at least one compound which is agriculturally active,and is individually coated with a monolamellar or oligolamellar layercomprising: (1) at least one non-ionic lipophilic surface-active agent,(2) at least one non-ionic hydrophilic surface-active agent and (3) atleast one ionic surface-active agent, wherein the globules having a meanparticle diameter of less than 800 nanometers. Further information onthe embodiment is disclosed in U.S. patent publication 20070027034published Feb. 1, 2007, having patent application Ser. No. 11/495,228.For ease of use, this embodiment will be referred to as “OIWE”.

For further information consult “Insect Pest Management” 2nd Edition byD. Dent, copyright CAB International (2000). Additionally, for moredetailed information consult “Handbook of Pest Control—The Behavior,Life History, and Control of Household Pests” by Arnold Mallis, 9thEdition, copyright 2004 by GIE Media Inc.

Other Formulation Components

Generally, when the molecules disclosed in Formula I are used in aformulation, such formulation can also contain other components. Thesecomponents include, but are not limited to, (this is a non-exhaustiveand non-mutually exclusive list) wetters, spreaders, stickers,penetrants, buffers, sequestering agents, drift reduction agents,compatibility agents, anti-foam agents, cleaning agents, andemulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases thespreading or penetration power of the liquid by reducing the interfacialtension between the liquid and the surface on which it is spreading.Wetting agents are used for two main functions in agrochemicalformulations: during processing and manufacture to increase the rate ofwetting of powders in water to make concentrates for soluble liquids orsuspension concentrates; and during mixing of a product with water in aspray tank to reduce the wetting time of wettable powders and to improvethe penetration of water into water-dispersible granules. Examples ofwetting agents used in wettable powder, suspension concentrate, andwater-dispersible granule formulations are: sodium lauryl sulfate;sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphaticalcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface ofparticles and helps to preserve the state of dispersion of the particlesand prevents them from reaggregating. Dispersing agents are added toagrochemical formulations to facilitate dispersion and suspension duringmanufacture, and to ensure the particles redisperse into water in aspray tank. They are widely used in wettable powders, suspensionconcentrates and water-dispersible granules. Surfactants that are usedas dispersing agents have the ability to adsorb strongly onto a particlesurface and provide a charged or steric barrier to reaggregation ofparticles. The most commonly used surfactants are anionic, non-ionic, ormixtures of the two types. For wettable powder formulations, the mostcommon dispersing agents are sodium lignosulfonates. For suspensionconcentrates, very good adsorption and stabilization are obtained usingpolyelectrolytes, such as sodium naphthalene sulfonate formaldehydecondensates. Tristyrylphenol ethoxylate phosphate esters are also used.Non-ionics such as alkylarylethylene oxide condensates and EO-PO blockcopolymers are sometimes combined with anionics as dispersing agents forsuspension concentrates. In recent years, new types of very highmolecular weight polymeric surfactants have been developed as dispersingagents. These have very long hydrophobic ‘backbones’ and a large numberof ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant.These high molecular weight polymers can give very good long-termstability to suspension concentrates because the hydrophobic backboneshave many anchoring points onto the particle surfaces. Examples ofdispersing agents used in agrochemical formulations are: sodiumlignosulfonates; sodium naphthalene sulfonate formaldehyde condensates;tristyrylphenol ethoxylate phosphate esters; aliphatic alcoholethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graftcopolymers.

An emulsifying agent is a substance which stabilizes a suspension ofdroplets of one liquid phase in another liquid phase. Without theemulsifying agent the two liquids would separate into two immiscibleliquid phases. The most commonly used emulsifier blends containalkylphenol or aliphatic alcohol with twelve or more ethylene oxideunits and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. Arange of hydrophile-lipophile balance (“HLB”) values from 8 to 18 willnormally provide good stable emulsions. Emulsion stability can sometimesbe improved by the addition of a small amount of an EO-PO blockcopolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in waterat concentrations above the critical micelle concentration. The micellesare then able to dissolve or solubilize water-insoluble materials insidethe hydrophobic part of the micelle. The types of surfactants usuallyused for solubilization are non-ionics, sorbitan monooleates, sorbitanmonooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additivessuch as mineral or vegetable oils as adjuvants to spray-tank mixes toimprove the biological performance of the pesticide on the target. Thetypes of surfactants used for bioenhancement depend generally on thenature and mode of action of the pesticide. However, they are oftennon-ionics such as: alkyl ethoxylates; linear aliphatic alcoholethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material addedto the pesticide to give a product of the required strength. Carriersare usually materials with high absorptive capacities, while diluentsare usually materials with low absorptive capacities. Carriers anddiluents are used in the formulation of dusts, wettable powders,granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiableconcentrates, oil-in-water emulsions, suspoemulsions, and ultra lowvolume formulations, and to a lesser extent, granular formulations.Sometimes mixtures of solvents are used. The first main groups ofsolvents are aliphatic paraffinic oils such as kerosene or refinedparaffins. The second main group (and the most common) comprises thearomatic solvents such as xylene and higher molecular weight fractionsof C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful ascosolvents to prevent crystallization of pesticides when the formulationis emulsified into water. Alcohols are sometimes used as cosolvents toincrease solvent power. Other solvents may include vegetable oils, seedoils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation ofsuspension concentrates, emulsions and suspoemulsions to modify therheology or flow properties of the liquid and to prevent separation andsettling of the dispersed particles or droplets. Thickening, gelling,and anti-settling agents generally fall into two categories, namelywater-insoluble particulates and water-soluble polymers. It is possibleto produce suspension concentrate formulations using clays and silicas.Examples of these types of materials, include, but are not limited to,montmorillonite, bentonite, magnesium aluminum silicate, andattapulgite. Water-soluble polysaccharides have been used asthickening-gelling agents for many years. The types of polysaccharidesmost commonly used are natural extracts of seeds and seaweeds or aresynthetic derivatives of cellulose. Examples of these types of materialsinclude, but are not limited to, guar gum; locust bean gum; carrageenam;alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC);hydroxyethyl cellulose (HEC). Other types of anti-settling agents arebased on modified starches, polyacrylates, polyvinyl alcohol andpolyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Thereforepreservation agents are used to eliminate or reduce their effect.Examples of such agents include, but are not limited to: propionic acidand its sodium salt; sorbic acid and its sodium or potassium salts;benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt;methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations tofoam during mixing operations in production and in application through aspray tank. In order to reduce the tendency to foam, anti-foam agentsare often added either during the production stage or before fillinginto bottles. Generally, there are two types of anti-foam agents, namelysilicones and non-silicones. Silicones are usually aqueous emulsions ofdimethyl polysiloxane, while the non-silicone anti-foam agents arewater-insoluble oils, such as octanol and nonanol, or silica. In bothcases, the function of the anti-foam agent is to displace the surfactantfrom the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce theoverall environmental footprint of crop protection formulations. Greenagents are biodegradable and generally derived from natural and/orsustainable sources, e.g. plant and animal sources. Specific examplesare: vegetable oils, seed oils, and esters thereof, also alkoxylatedalkyl polyglucosides.

For further information, see “Chemistry and Technology of AgrochemicalFormulations” edited by D. A. Knowles, copyright 1998 by Kluwer AcademicPublishers. Also see “Insecticides in Agriculture andEnvironment—Retrospects and Prospects” by A. S. Perry, I. Yamamoto, I.Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

Pests

In general, the molecules of Formula I may be used to control pests e.g.beetles, earwigs, cockroaches, flies. aphids, scales, whiteflies,leafhoppers, ants, wasps, termites, moths, butterflies, lice,grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites,ticks, nematodes, and symphylans.

In another embodiment, the molecules of Formula I may be used to controlpests in the Phyla Nematoda and/or Arthropoda.

In another embodiment, the molecules of Formula I may be used to controlpests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.

In another embodiment, the molecules of Formula I may be used to controlpests in the Classes of Arachnida, Symphyla, and/or Insecta.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Anoplura. A non-exhaustive list of particular generaincludes, but is not limited to, Haematopinus spp., Hoplopleura spp.,Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustivelist of particular species includes, but is not limited to, Haematopinusasini, Haematopinus suis, Linognathus setosus, Linognathus ovillus,Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.

In another embodiment, the molecules of Formula I may be used to controlpests in the Order Coleoptera. A non-exhaustive list of particulargenera includes, but is not limited to, Acanthoscelides spp., Agriotesspp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp.,Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp.,Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp.,Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp.,Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp.,Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp.,Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp.,and Tribolium spp. A non-exhaustive list of particular species includes,but is not limited to, Acanthoscelides obtectus, Agrilus planipennis,Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus,Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum,Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata,Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi,Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinisnitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestespusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporausmarginatus, Dermestes lardarius, Dermestes maculatus, Epilachnavarivestis, Faustinus cubae, Hylobius pales, Hypera postica,Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata,Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus,Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolonthamelolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros,Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus,Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanustruncatus, Rhyzopertha dominica, Sitona lineatus, Sitophilus granarius,Sitophilus oryzae, Sitophilus zeamais, Step gobium paniceum, Triboliumcastaneum, Tribolium confusum, Trogoderma variabile, and Zabrustenebrioides.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Dermaptera.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Blattaria. A non-exhaustive list of particularspecies includes, but is not limited to, Blattella germanica, Blattaorientalis, Parcoblatta pennsylvanica, Periplaneta americana,Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa,Pycnoscelus surinamensis, and Supella longipalpa.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Diptera. A non-exhaustive list of particular generaincludes, but is not limited to, Aedes spp., Agromyza spp., Anastrephaspp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp.,Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Deliaspp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Muscaspp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive listof particular species includes, but is not limited to, Agromyzafrontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa,Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens,Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Deliaplatura, Fannia canicularis, Fannia scalaris, Gasterophilusintestinalis, Gracillia perseae, Haematobia irritans, Hypodermalineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis,Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psilarosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax,Sitodiplosis mosellana, and Stomoxys calcitrans.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Hemiptera. A non-exhaustive list of particular generaincludes, but is not limited to, Adelges spp., Aulacaspis spp.,Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspisspp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp.,Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezaraspp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcusspp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphisspp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp.and Unaspis spp. A non-exhaustive list of particular species includes,but is not limited to, Acrosternum hilare, Acyrthosiphon pisum,Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus,Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphisglycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisiatabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi,Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimexhemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus,Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercussuturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura,Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltistheivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus,Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus,Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium,Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata,Metopolophium dirhodum, Mictis longicomis, Myzus persicae, Nephotettixcinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvatalugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis,Phylloxera vitifoliae, Physokermes piceae, Phytocoris californicus,Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus,Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes,Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi,Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobionavenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodesabutiloneus, Unaspis yanonensis, and Zulia entrerriana.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Hymenoptera. A non-exhaustive list of particulargenera includes, but is not limited to, Acromyrmex spp., Atta spp.,Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprionspp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp.,and Xylocopa spp. A non-exhaustive list of particular species includes,but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis,Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsisgeminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni,and Tapinoma sessile.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Isoptera. A non-exhaustive list of particular generaincludes, but is not limited to, Coptotermes spp., Cornitermes spp.,Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermesspp., Macrotermes spp., Marginitermes spp., Microcerotermes spp.,Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., andZootermopsis spp. A non-exhaustive list of particular species includes,but is not limited to, Coptotermes curvignathus, Coptotermes frenchi,Coptotermes formosanus, Heterotermes aureus, Microtermes obesi,Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermesflavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermessantonensis, Reticulitermes speratus, Reticulitermes tibialis, andReticulitermes virginicus.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Lepidoptera. A non-exhaustive list of particulargenera includes, but is not limited to, Adoxophyes spp., Agrotis spp.,Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp.,Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraeaspp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortynaspp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletisspp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycterspp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp.,and Yponomeuta spp. A non-exhaustive list of particular speciesincludes, but is not limited to, Achaea janata, Adoxophyes orana,Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyeloistransitella, Anacamptodes defectaria, Anarsia lineatella, Anomissabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana,Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbocinnara, Bucculatrix thurberiella, Capua reticulana, Carposinaniponensis, Chlumetia transversa, Choristoneura rosaceana,Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydiacaryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydiapomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella,Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpuslignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella,Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoeciliaambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata,Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellulaundalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucopteracoffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotisalbicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti,Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta,Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata,Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemisheparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia,Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistiscitrella, Pieris rapae, Plathypena scabra, Plodia interpunctella,Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae,Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu,Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setoranitens, Sitotroga cerealella, Sparganothis pilleriana, Spodopteraexigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides,Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae,and Zeuzera pyrina.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Mallophaga. A non-exhaustive list of particulargenera includes, but is not limited to, Anaticola spp., Bovicola spp.,Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp.A non-exhaustive list of particular species includes, but is not limitedto, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistesmeleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthusstramineus, Menopon gallinae, and Trichodectes canis.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Orthoptera. A non-exhaustive list of particulargenera includes, but is not limited to, Melanoplus spp., and Pterophyllaspp. A non-exhaustive list of particular species includes, but is notlimited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpaaustralis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locustamigratoria, Microcentrum retinerve, Schistocerca gregaria, and Scudderiafurcata.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Siphonaptera. A non-exhaustive list of particularspecies includes, but is not limited to, Ceratophyllus gallinae,Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis, andPulex irritans.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Thysanoptera. A non-exhaustive list of particulargenera includes, but is not limited to, Caliothrips spp., Frankliniellaspp., Scirtothrips spp., and Thrips spp. A non-exhaustive list ofparticular sp. includes, but is not limited to, Frankliniella fusca,Frankliniella occidentalis, Frankliniella schultzei, Frankliniellawilliamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus,Scirtothrips citri, Scirtothrips dorsalis, and Taeniothripsrhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thripsorientalis, Thrips tabaci.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Thysanura. A non-exhaustive list of particular generaincludes, but is not limited to, Lepisma spp. and Thermobia spp.

In another embodiment, the molecules of Formula I may be used to controlpests of the Order Acarina. A non-exhaustive list of particular generaincludes, but is not limited to, Acarus spp., Aculops spp., Boophilusspp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp.,Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., andTetranychus spp. A non-exhaustive list of particular species includes,but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae,Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyommaamericanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentorvariabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini,Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychuscitri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemuslatus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophusperseaflorae, Tetranychus urticae, and Varroa destructor.

In another embodiment, the molecules of Formula I may be used to controlpest of the Order Symphyla. A non-exhaustive list of particular sp.includes, but is not limited to, Scutigerella immaculata.

In another embodiment, the molecules of Formula I may be used to controlpests of the Phylum Nematoda. A non-exhaustive list of particular generaincludes, but is not limited to, Aphelenchoides spp., Belonolaimus spp.,Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniellaspp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., andRadopholus spp. A non-exhaustive list of particular sp. includes, but isnot limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyneincognita, Meloidogyne javanica, Onchocerca volvulus, Radopholussimilis, and Rotylenchulus reniformis.

For additional information consult “HANDBOOK OF PEST CONTROL—THEBEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by ArnoldMallis, 9th Edition, copyright 2004 by GIE Media Inc.

Applications

Molecules of Formula I are generally used in amounts from about 0.01grams per hectare to about 5000 grams per hectare to provide control.Amounts from about 0.1 grams per hectare to about 500 grams per hectareare generally preferred, and amounts from about 1 gram per hectare toabout 50 grams per hectare are generally more preferred.

The area to which a molecule of Formula I is applied can be any areainhabited (or maybe inhabited, or traversed by) a pest, for example:where crops, trees, fruits, cereals, fodder species, vines, turf andornamental plants, are growing; where domesticated animals are residing;the interior or exterior surfaces of buildings (such as places wheregrains are stored), the materials of construction used in building (suchas impregnated wood), and the soil around buildings. Particular cropareas to use a molecule of Formula I include areas where apples, corn,sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley,oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes,peppers, crucifers, pears, tobacco, almonds, sugar beets, beans andother valuable crops are growing or the seeds thereof are going to beplanted. It is also advantageous to use aluminum sulfate with a moleculeof Formula I when growing various plants.

Controlling pests generally means that pest populations, pest activity,or both, are reduced in an area. This can come about when: pestpopulations are repulsed from an area; when pests are incapacitated inor around an area; or pests are exterminated, in whole, or in part, inor around an area. Of course, a combination of these results can occur.Generally, pest populations, activity, or both are desirably reducedmore than fifty percent, preferably more than 90 percent. Generally, thearea is not in or on a human; consequently, the locus is generally anon-human area.

The molecules of Formula I may be used in mixtures, appliedsimultaneously or sequentially, alone or with other compounds to enhanceplant vigor (e.g. to grow a better root system, to better withstandstressful growing conditions). Such other compounds are, for example,compounds that modulate plant ethylene receptors, most notably1-methylcyclopropene (also know as 1-MCP).

The molecules of Formula I can be applied to the foliar and fruitingportions of plants to control pests. The molecules will either come indirect contact with the pest, or the pest will consume the pesticidewhen eating leaf, fruit mass, or extracting sap, that contains thepesticide. The molecules of Formula I can also be applied to the soil,and when applied in this manner, root and stem feeding pests can becontrolled. The roots can absorb a molecule taking it up into the foliarportions of the plant to control above ground chewing and sap feedingpests.

Generally, with baits, the baits are placed in the ground where, forexample, termites can come into contact with, and/or be attracted to,the bait. Baits can also be applied to a surface of a building,(horizontal, vertical, or slant surface) where, for example, ants,termites, cockroaches, and flies, can come into contact with, and/or beattracted to, the bait. Baits can comprise a molecule of Formula I.

The molecules of Formula I can be encapsulated inside, or placed on thesurface of a capsule. The size of the capsules can range from nanometersize (about 100-900 nanometers in diameter) to micrometer size (about10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resistcertain pesticides, repeated applications of the molecules of Formula Imay be desirable to control newly emerged larvae.

Systemic movement of pesticides in plants may be utilized to controlpests on one portion of the plant by applying (for example by sprayingan area) the molecules of Formula I to a different portion of the plant.For example, control of foliar-feeding insects can be achieved by dripirrigation or furrow application, by treating the soil with for examplepre- or post-planting soil drench, or by treating the seeds of a plantbefore planting.

Seed treatment can be applied to all types of seeds, including thosefrom which plants genetically modified to express specialized traitswill germinate. Representative examples include those expressingproteins toxic to invertebrate pests, such as Bacillus thuringiensis orother insecticidal toxins, those expressing herbicide resistance, suchas “Roundup Ready” seed, or those with “stacked” foreign genesexpressing insecticidal toxins, herbicide resistance,nutrition-enhancement, drought resistance, or any other beneficialtraits. Furthermore, such seed treatments with the molecules of FormulaI may further enhance the ability of a plant to better withstandstressful growing conditions. This results in a healthier, more vigorousplant, which can lead to higher yields at harvest time. Generally, about1 gram of the molecules of Formula I to about 500 grams per 100,000seeds is expected to provide good benefits, amounts from about 10 gramsto about 100 grams per 100,000 seeds is expected to provide betterbenefits, and amounts from about 25 grams to about 75 grams per 100,000seeds is expected to provide even better benefits.

It should be readily apparent that the molecules of Formula I may beused on, in, or around plants genetically modified to expressspecialized traits, such as Bacillus thuringiensis or other insecticidaltoxins, or those expressing herbicide resistance, or those with“stacked” foreign genes expressing insecticidal toxins, herbicideresistance, nutrition-enhancement, or any other beneficial traits.

The molecules of Formula I may be used for controlling endoparasites andectoparasites in the veterinary medicine sector or in the field ofnon-human animal keeping. The molecules of Formula I are applied, suchas by oral administration in the form of, for example, tablets,capsules, drinks, granules, by dermal application in the form of, forexample, dipping, spraying, pouring on, spotting on, and dusting, and byparenteral administration in the form of, for example, an injection.

The molecules of Formula I may also be employed advantageously inlivestock keeping, for example, horses, cattle, sheep, pigs, chickens,and geese. They may also be employed advantageously in pets such as,horses, dogs, and cats. Particular pests to control would be fleas andticks that are bothersome to such animals. Suitable formulations areadministered orally to the animals with the drinking water or feed. Thedosages and formulations that are suitable depend on the species.

The molecules of Formula I may also be employed in therapeutic methodsfor human health care. Such methods include, but are limited to, oraladministration in the form of, for example, tablets, capsules, drinks,granules, and by dermal application.

Before a pesticide can be used or sold commercially, such pesticideundergoes lengthy evaluation processes by various governmentalauthorities (local, regional, state, national, and international).Voluminous data requirements are specified by regulatory authorities andmust be addressed through data generation and submission by the productregistrant or by a third party on the product registrant's behalf, oftenusing a computer with a connection to the World Wide Web. Thesegovernmental authorities then review such data and if a determination ofsafety is concluded, provide the potential user or seller with productregistration approval. Thereafter, in that locality where the productregistration is granted and supported, such user or seller may use orsell such pesticide.

The headings in this document are for convenience only and must not beused to interpret any portion hereof.

TABLE 1 Compound MS (ESIMS Number Appearance mp (° C.) IR m/z) MOLECULARSTRUCTURE 22 pale yellow solid 162-163 234.0 (M + 1)

23 pale yellow solid 102-105 276.2 (M + 1)

24 pale yellow solid 113-114 262.2 (M + 1)

25 pale yellow solid 126-128 302.0 (M + 1)

26 pale yellow solid 173-175 297.0 (M + 1)

27 pale yellow solid 127-129 306.2 (M + 1)

28 light yellow solid  98-100 307.9 (M + 1)

29 white solid 92-94 322.2 (M + 1)

30 white solid 111-114 312.1 (M + 1)

31 orange solid 75-77 326.1 (M + 1)

32 white solid 156-158 279.9 (M + 1)

33 tan solid 153-155 293.8 (M + 1)

34 white solid 83-88 336.2 (M + 1)

35 clear oil 2918, 1674, 1553 308.2 (M + 1)

36 light yellow oil 2973, 2917, 1675, 1554 322.2 (M + 1)

37 clear orange oil 2917, 2934, 1676, 1554 275.9 (M + 1)

38 colorless oil 1679 326.2 (M + 1)

39 colorless oil 1663 354.3 (M + 1)

40 yellow oil 1676 340.2 (M + 1)

41 yellow solid 123 294.2 (M + 1)

42 yellow oil 1697 336.2 (M + 1)

43 yellow oil 1686 362 (M + 1)

44 yellow oil 1688 376 (M + 1)

45 clear colorless oil 1663 390.4 (M + 1)

46 clear yellow oil 1694 332.3 (M + 3)

47 yellow gum 1678 324.4 (M + 3)

48 yellow gum 291.59 (M + 2)

49 yellow gum 1656, 1684 352.3 (M + 2)

50 yellow gum 1676 336.0 (M + 1)

51 yellow oil 1679 310.5 (M + 2)

52 yellow- orange oil 1676 324.5 (M + 2)

53 yellow solid 123-125 338.6 (M + 2)

54 white solid 108-109 378.5 (M + 2)

55 yellow solid 136-139 1668, 1573 291.9 (M − 1)

56 orange solid 132-136 308.2 (M + 1)

57 orange oil 1671, 1560 322.2 (M + 1)

58 yellow solid 159-162 261.9 (M + 1)

59 beige gum 1686, 1715 338.4 (M + 3)

60 yellow gum 1674 350.3 (M + 1)

61 orange gum 1675 384.3 (M + 1)

62 brown gum 1672 397.13 (M+)

63 gold gum 1713, 1676 353.66 (M + 2)

64 yellow solid 86-88 1711 265.98 (M − 1)

65 yellow green gum 1677 369.1 (M+)

66 beige gum 1682 320.29 (M + 1)

67 brown gum 1674 383.11 (M+)

68 light brown solid 104-108 1623 356.1 (M + 1)

69 light yellow solid 155-159 1643 296.1 (M + 1)

70 beige solid 160-164 328.1 (M + 1)

71 white solid 182-186 280.1 (M + 1)

79 tan solid 135-140 324.1 (M + 1)

80 white solid 118-122 338.1 (M + 1)

81 dark green 68-70 342.1 (M + 1)

82 yellow solid 202-203 343.1 (M + 1)

83 yellow solid 95-99 357.1 (M + 1)

84 white solid 153-155 344.1 (M + 1)

85 yellow solid 155-159 356.2 (M + 1)

86 colorless oil 1677 355.8 (M + 1)

87 yellow oil 1674 338.2 (M + 1)

88 yellow oil 1684 378.2 (M + 1)

89 yellow oil 1682 392.3 (M + 1)

90 white oil 1674 324.2 (M + 1)

91 yellow syrup 1675 342.2 (M + 1)

92 white solid 160-163 323.9 (M + 1)

93 yellow solid 171-173 307.8 (M + 1)

94 yellow foam 55-60 338.5 (M + 1)

96 colorless oil 1676 360.3 (M + 1)

97 milky white oil 1648 368.3 (M + 1)

98 white solid 105-109 372.2 (M + 1)

99 white solid 175-180 340.2 (M + 1)

100 white solid 222-224 326.1 (M + 1)

101 yellow solid 134-136 354.4 (M + 1)

120 Thick beige gum 1720 332.0 (M + 3)

133 white solid 131-133 346.1 (M − 1)

134 orange oil 1556 360.1 (M − 1)

135 orange oil 1555 374.2 (M − 1)

136 white solid 130-131 314.2 (M − 1)

137 viscous yellow oil 3258, 2971, 2918, 1710 338.2 (M + 1)

138 Yellow gum 1674 349.51 (M + 2)

139 orange oil 1558 340.5 (M + 1)

140 yellow solid 155-159 280.4 (M + 1)

141 orange- solid solid 110-113 323.9 (M − 1)

142 white solid 126-130 309.9 (M − 1)

143 white solid 160-163 353.9 (M − 1)

144 white solid 157-167 369.9 (M − 1)

145 white solid 194-198 342.1 (M + 1)

146 white solid 187-189 358.1 (M + 1)

147 white solid 181-184 325.9 (M − 1)

148 white solid 230-232 341.9 (M − 1)

149 light yellow solid 154-157 326.2 (M + 1)

150 dark yellow solid 135-138 304.2 (M + 1)

151 orange solid 171-174 317.2 (M + 1)

152 yellow gum 1713 456.1 (M + 1)

153 light yellow solid 82-85 442.1 (M + 1)

154 yellow oil 1744, 1714 426.2 (M + 1)

155 yellow oil 1743, 1725 480.2 (M + 1)

156 orange oil 1743, 1713 422.2 (M + 1)

157 orange gum 1744, 1711 486.2 (M + 1)

158 white solid 125-128 433.2 (M + 1)

159 off -white solid 143-146 325.8 (M + 1)

160 orange solid 124-128 364.5 (M + 1)

161 white solid 168-172 387.1 (M + 1)

162 light yellow oil 1722 350.2 (M + 1)

163 light yellow solid 75-81 365.93 (M + 1)

164 light yellow solid

165 white semisolid 1714.54 324.43 (M + 1)

166 yellow oil 1671.41 432.5 (M + 1)

167 clear oil 508.36 (M + 1)

168 clear oil 397.4 (M + 2)

169 light yellow solid 142-146 342.1 (M + 1)

170 dark orange gum 3214, 2979, 2919, 1712 379.9 (M + 1)

171 yellow gum 2973, 2920 322.5 (M + 1)

172 yellow solid 127-131 333.1 (M + 1)

173 dark orange oil 1715 424.2 (M + 1)

174 Yellow gum 1681 343.74 (M − 2)

175 beige solid 136-140 322.5 (M + 1)

176 dark yellow oil 1743, 1713 438.5 (M + 1)

177 yellow solid 115-119 324.5 (M + 2)

178 tan solid 145-146 324.5 (M + 1)

179 yellow oil 1648.92 309.4 (M + 1)

180 yellow semisolid 2972, 2918 324.12 (M + 1)

181 white solid 123-126 311.89 (M + 2)

182 light yellow semisolid 1711.82 437.8 (M + 1)

183 dark orange oil 1720 377.9 (M + 1)

184 orange oil 1712 350.5 (M + 1)

185 yellow oil 1721 414.1 (M + 1)

186 light yellow solid 180-182 235.1 (M + 1)

187 light yellow solid 166-169 362.9 (M + 1)

188 light yellow oil 1713 442.1 (M + 1)

189 orange oil 1723 423.2 (M + 1)

190 yellow oil 451.4 (M + 1)

191 yellow solid 140-143 347.9 (M + 1)

192 yellow oil 1712.68 321.4 (M + 1)

193 yellow solid 127-130 249.1 (M + 1)

194 semi-solid orange 1708, 1679 377.1 (M + 1)

195 light oil orange 1707 439.2 (M + 1)

196 light orange oil 1684 351.9 (M + 1)

197 light yellow solid 151-153 306.5 (M + 1)

198 yellow oil 1711.53 331.99 (M + 1)

199 yellow solid 120-123 322.5 (M + 1)

200 yellow oil 1719 396.2 (M + 1)

201 white solid 137-139 324.1 (M − 1)

202 white solid 159-160 248.1 (M − 1)

203 light yellow oil 1721, 1694 442.1 (M + 1)

204 orange oil 1710 362.0 (M + 1)

205 beige solid 68-70 346.5 (M + 1)

206 yellow oil 1671 320.1 (M + 1)

207 yellow oil 1740, 1694 409.2 (M + 1)

208 yellow solid 165-167 247.1 (M + 1)

209 yellow solid 144-147 296.1 (M + 1)

210 yellow oil 1671 336.2 (M + 1)

211 orange semi- solid 1695 259.9 (M + 1)

212 white solid 73-80 354.2 (M + 1)

213 yellow oil 1670.97 340.2 (M + 1)

214 yellow semi solid 1661.6 338.1

215 yellow oil 1673.26 354.2 (M + 1)

216 white solid 88-90 338.1 (M + 1)

217 off white solid 123-126 340.2 (M + 1)

218 off white solid 130-133 326.1 (M + 1)

219 yellow solid 209-213 324.1 (M + 1)

220 dark yellow solid 206-212 324.1 (M + 1)

221 yellow oil 1671 398.2 (M + 1)

222 yellow oil 1699 350.2 (M + 1)

223 thick yellow gum 1672 364.2 (M + 1)

224 yellow oil 3039, 2975, 2938, 1635 334.1 (M + 1)

225 pale yellow solid 147-149 349.9 (M + 1)

226 orange solid 76-79 352.2 (M + 1)

227 yellow oil 1681 342.2 (M + 1)

228 yellow solid 119-122 326.2 (M + 1)

229 yellow solid 170-174 368.2 (M + 1)

230 clear gum 1678 358.2 (M + 1)

231 clear oil 1686 296.2 (M + 1)

232 pale yellow oil 1746, 1679 334.3 (M + 1)

233 pale yellow oil 1676 290.2 (M + 1)

234 clear oil 1660 352.2 (M + 1)

235 pale yellow oil 1668 368.3 (M + 1)

236 pale yellow oil 1675 322.2 (M + 1)

237 dark red oil 1650 350.3 (M + 1)

238 white solid 89-92 1672 338.3 (M + 1)

239 clear oil 1674 354.2 (M + 1)

240 dark red oil 1675 354.3 (M + 1)

241 tan solid 104-107 326.1 (M + 1)

242 white solid 88-91 372.1 (M + 2)

243 yellow solid 148-151 1682 310.2 (M + 1)

244 beige solid 124-126 397.9 (M + 1)

245 light pink solid 89-92 323.8 (M + 1)

246 clear viscous oil 1684 362.5 (M + 1)

247 light yellow oil 1680 377.3 (M + 1)

248 dark oil 1684.18 342.1 (M + 1)

249 clear oil 1641 387.9 (M + 1)

250 clear oil 1646 382.9 (M + 1)

251 white solid 74-76 386.2 (M + 2)

252 clear oil 1715 320.3 (M + 1)

253 orange solid 1678 308.6 (M + 1)

254 light red oil 1675 341.6 (M + 1)

255 red oil 1653 368.6 (M + 1)

256 pale yellow oil 1673 356.2 (M + 1)

257 pale yellow oil 1675 372.2 (M + 1)

258 yellow oil 1670 370.2 (M + 1)

259 clear solid 148.7-156. 9 1676 386.2 (M + 1)

260 light yellow oil 1645 384.2 (M + 1)

261 clear oil 1648 400.2 (M + 1)

262 yellow oil 1684 360.2 (M + 1)

263 light yellow solid 123-125 314.2 (M + 1)

264 light yellow solid 103-106 356.2 (M + 1)

265 pink solid 98-99 398.3 (M + 1)

266 yellow oil 1698 346.2 (M + 1)

267 dark red oil 1718 358.2 (M + 1)

268 yellow solid 151-155 352.2 (M + 1)

269 clear gum 1653 372.2 (M + 1)

270 light yellow gum 1680 376.2 (M + 1)

271 white solid 151-154 1686 392.2 (M + 1)

272 beige solid 123-126 362.2 (M + 1)

273 yellow gum 1684 378.1 (M + 1)

274 red oil 1684 360.2 (M + 1)

275 red oil 1685 328.2 (M + 1)

276 orange oil 1713, 1692 363.3 (M + 1)

277 off white solid 94-96 396.3 (M + 1)

278 red oil 1660 388.2 (M + 1)

279 orange oil 1681 374.2 (M + 1)

280 clear gum 1709, 1672 453.4 (M + 1)

281 yellow oil 1710, 1678 437.3 (M + 1)

282 yellow gum 377.3 (M + 1)

283 pale yellow oil 1710, 1677

284 yellow oil 1729.59 334.3 (M + 1)

285 clear oil 1675.42 356.2 (M + 1)

286 clear oil 1674.32 350.3 (M + 1)

287 clear oil 1677.01 356.2 (M + 1)

288 orange gum 1682 376.2 (M + 1)

289 colorless gum 1687 390.2 (M + 1)

290 pale yellow oil 1711, 1678 499.4 (M + 1)

291 yellow gum 1707, 1675 568.5 (M + 1)

292 yellow oil 1695 403.3 (M + 1)

293 red oil 1712, 1674 497.4 (M + 1)

294 clear gum 1684 391.3 (M + 1)

295 clear oil 1671 291.3 (M + 1)

296 yellow solid 79-81 402.2 (M + 2)

297 white solid 164-166 376.2 (M + 1)

298 white solid 160-163 378.1 (M + 2)

299 yellow gum 3163, 3057, 2919, 1679 391.9 (M + 2)

300 yellow oil 354.3 (M + 1)

301 yellow oil 1714.5 338.3 (M + 1)

302 oil 1713.23 336.3 (M + 1)

303 pale yellow oil 1720 403.2 (M + 1)

304 red oil 1718 340.3 (M + 1)

305 red oil 1679 342.2 (M + 1)

306 white solid 172-175 408.1 (M + 2)

307 beige solid 185-188 424 (M + 2)

308 beige solid 78-81 326.2 (M + 1)

309 pale yellow crystalline solid 160-161 310.1 (M + 1)

310 yellow oil 1712, 1680 484.4 (M + 1)

311 clear oil 1711, 1692 405.4 (M + 1)

312 pale yellow oil 1711, 1679 391.4 (M + 1)

313 red oil 1680 342.2 (M + 1)

314 orange oil 1680 358.3 (M + 1)

315 yellow oil 1681 374.3 (M + 1)

316 orange oil 79-81 356.3 (M + 1)

317 off white solid 154-156 476.2 (M + 2)

318 tan solid 108-110 390.2 (M + 2)

319 yellow oil 1676.65 354.3 (M + 1)

320 brownish oil 1673.91 398.3 (M + 1)

321 brownish oil 1674.03 384.3 (M + 1)

322 yellow oil 1675.46 336.3 (M + 1)

323 yellow oil 1676.25 350.6 (M + 1)

324 brown oil 1681.22 356.2 (M + 1)

325 yellow solid 106-111 308.3 (M + 1)

326 2979, 2938, 1718, 1670 344.2 (M + 1)

327 1718, 1675 358.3 (M + 1)

328 1678 378.2 (M + 1)

329 3197, 2917, 1665 384.2 (M + 1)

330 1669 398.3 (M + 1)

331 1677 418.2 (M + 1)

332 3247, 2985, 1697 357.3 (M + 1)

333 1678 391.2 (M + 1)

334 3448, 1748 306.2 (M + 1)

335 1743, 1692 320.3 (M + 1)

336 1742, 1699 340.2 (M + 1)

337 3209, 2976, 1682, 1661 375.3 (M + 1)

338 1701 389.3 (M + 1)

339 1669 409.2 (M + 1)

340 3346, 1669 303.2 (M + 1)

341 1658 337.1 (M + 1)

342 3389, 1667 287.2 (M + 1)

343 1665 301.2 (M + 1)

344 3167, 2937, 1641 303.2 (M + 1)

345 1654 317.2 (M + 1)

346 1659 337.1 (M + 1)

347 3173, 2975, 1658, 1637 344.2 (M + 1)

348 yellow oil 1679 372.2 (M + 1)

349 white solid 152-154 388.2 (M + 1)

350 yellow oil 1668, 1643 358.2 (M + 1)

351 pale yellow oil 1669, 1640 378.2 (M + 1)

352 off white solid 125-128 430.2 (M + 1)

353 pale yellow solid 188-191 258.1 (M + 1)

354 red oil 1682 406.1 (M + 1)

355 pale yellow solid 219-222 300.3 (M + 1)

356 white solid 72-76 333 (M + 2)

357 tan oil 394 (M + 1)

358 brown oil 1673 308 (M + 1)

359 tan solid 135-138 1665 294 (M + 1)

360 tacky tan solid 1673 308 (M + 1)

361 tan solid  97-104 1663 328 (M + 1)

363 pale yellow oil 1685 336.3 (M + 1)

364 yellow gum 3258, 3072, 2977, 2919, 1682 346.2 (M + 1)

365 yellow oil 1655 317.2 (M + 1)

366 yellow solid 81-84 328.2 (M + 1)

367 yellow oil 1672 294.4 (M + 1)

368 brown oil 1677 322 (M + 1)

369 tan solid 111-114 1661 316 (M + 2)

370 tan solid 68-71 1667 328.2 (M + 1)

371 brown oil 1684 344 (M + 2)

372 light yellow solid 164-167 1674 282.4 (M + 2)

373 yellow solid 157-158 1668 294 (M + 1)

374 yellow solid 110-112 1642 308 (M + 1)

375 yellow solid 163-167 319.3 (M + 2)

376 light yellow solid 88-94 306.3 (M + 1)

377 yellow solid 108-110 292 (M + 1)

378 yellow solid 133-137 332.3 (M + 1)

379 yellow solid 131-134 294.2 (M + 1)

380 yellow solid 170-178 318.2 (M + 1)

381 fluffy yellow solid 158-159 376.2, 378.2

382 pale yellow oil 412.2

383 rust colored solid 121-124 349.2

384 orange oil 1684 331.4 (M + 1)

385 yellow oil 1683 345.5 (M + 1)

386 white solid 163-164 307.3

387 pale yellow solid 129-130 315.3, 314.3

388 pale yellow solid 190-194 395.4, 393.4

389 off-white solid 214-215 435

390 off-white solid 185-186 468.08

391 yellow solid 150-151 290.12

392 white solid 113-116 346.1 (M + 1)

393 pale yellow gum 1682 381.9 (M + 1)

394 orange glass 1675 429.3

395 white solid  93-101 366.1 (M + 1)

396 off-white solid 97-98 331

397 tan oil 1663 391.06

398 white solid 53-54 374.04

399 1653.05 286.2 (M + 1)

400 1658.56 300.2 (M + 1)

401 1668.99 320.2 (M + 1)

402 1657.88 372.3 (M + 1)

403 1664.94 392.2 (M + 1)

404 1662.35 342.3 (M + 1)

405 1673.28 362.2 (M + 1)

406 1665 311.3 (M + 1)

407 1674 345.2 (M + 1)

408 1660.22 346.2 (M + 1)

409 1713.63 380.2 (M + 1)

410 1668.86 387.3 (M + 1)

411 1676.13 407.3 (M + 1)

412 1668.23 359.3 (M + 1)

413 1675.32 379.3 (M + 1)

414 1648 345.3 (M + 1)

415 324.2 (M + 1)

416 1668.03 288.3 (M + 1)

417 1672.2 274.2 (M + 1)

418 1672.45 288.3 (M + 1)

420 tan glass 1695 451.2

421 off-white solid 153-154 332, 330

422 beige solid 114-117 378.3 (M + 1)

423 yellow oil 1718 342.3 (M + 1)

424 orange gum 1684 312.3 (M + 1)

425 yellow oil 1684 344.2 (M + 1)

426 tan oil 348 (M + 1)

427 yellow oil 1676 360.2

428 1708 438 (M + 1)

429 1652 385 (M + 1)

430 1689 399 (M + 1)

431 1695 419 (M + 1)

432 1691 311 (M + 1)

433 1686 355 (M + 1)

434 1696 375 (M + 1), 377 (M + 3)

435 1683 429 (M + 1)

436 1688 443 (M + 1)

437 1695 463 (M + 1)

438 1670 373 (M + 1)

439 1702 426 (M + 2)

440 1692 445 (M + 1)

441 orange oil 1686 392.1 (M + 2)

442 yellow oil 1675.84

443 white solid 1673.55 375.84 (M + 2)

444 white solid 1673.04 375.8 (M + 2)

445 orange oil 1677.42 357.87 (M + 1)

446 dark oil 1683.62 375.8 (M + 2)

447 dark oil 1685.07 387.9 ( (M + 1)

448 dark oil 1675.15 372.06 (M + 1)

449 orange solid 137-140

450 brown solid 361.98

451 fluffy white solid 184-185 348, 346

452 orange oil 1717 384.1 (M + 2)

453 oil 1685 346.2 (M + 1)

454 white solid 170-173 408 (M + 1)

455 off-white solid 198-201 424.1 (M + 1)

456 yellow oil 1682 358.3 (M + 1)

457 orange oil 1683 356.2 (M + 2)

458 yellow oil 1683 388.2 (M + 2)

459 white solid 239-240 364, 362

460 tan oil 1713 350 (M + 1)

461 tan oil 383 (M + 2)

462 tan oil 347 (M + 2)

463 tan oil 347 (M + 2)

464 brown oil 406 (M + 1)

465 tan oil 366 (M + 1)

466 light yellow oil 1674 362 (M + 2)

467 Tan Oil 1677 400 (M + 2)

468 tan oil 1674 362 (M + 1)

469 light yellow oil 1684 362.1 (M + 1)

470 white solid 42-46 1672 378.1 (M + 1)

471 clear oil 321.8 (M + 1)

472 orange oil 349.5 (M + 1)

473 yellow oil 1683 394.2 (M + 1)

474 light yellow solid 30-35 1682 410.1 (M + 1)

475 white solid 55-61 1683 426 (M + 1)

476 light yellow solid 119-120 1723.48 344.53 (M + 1)

477 brown reddish solid 65-67 306.1 (M + 1)

478 dark yellow solid 184-186 296.2 (M + 1)

480 orange oil 1682 402.1 (M + 2)

481 dirt yellow solid 148-149 422.1 (M + 1), 420.2 (M − 1),

482 yellow oil 1715.43 320.3 (M + 1)

483 yellow oil 1719.48 306.3 (M + 1)

484 yellow oil 1716.41 322.2 (M + 1)

485 yellow oil 1719.95 308.2 (M + 1)

486 yellow oil 1737.4 332.2 (M + 1)

487 brown solid 120-125 328.1 (M + 1)

488 tan solid 113-115 342.2 (M + 1)

489 yellow semi solid 1678.14 356.1 (M + 1)

490 yellow oil 1683.6 370.1 (M + 1)

491 yellow solid 65-69 334.2 (M + 1)

492 yellow oil 1731.07 360.4 (M + 1)

493 yellow oil 1715.81 346.2 (M + 1)

494 yellow solid 105-106 423.2 (M + 1), 422.1 (M − 1);

495 yellow solid 219-220 323.1 (M + 1), 322.1 (M − 1);

496 brown oil 444.2 (M + 1)

497 yellow solid 70-71 436.1 (M + 1)

498 orange oil 1683 374 (M + 2)

499 dark orange oil 1684 388 (M + 2)

500 light yellow oil 1686 362.1 (M + 1)

501 colorless oil 1684 378 (M + 1)

502 yellow solid 231-232 275.1 (M + 1), 273.1 (M − 1)

503 yellow solid 97-98 336.1 (M + 1)+;

504 yellow foam 1681 404 (M + 2)

505 red oil 1681 388 (M + 2)

506 yellow oil 1682 390 (M + 2)

507 white foam 1683 406 (M + 2)

508 red oil 1684, 2237 353.0 (M + 1)

509 light yellow oil 1674 329.1 (M + 1)

510 white solid 137-140 1684 345.1 (M + 1)

511 sticky orange- brown solid 1513 377, 375

512 brown oil 1521 457, 455

513 light yellow oil 1648 358.1 (M + 1)

514 white amorphous solid 1683 374.1 (M + 1)

515 off-white solid 74-76 1648 346.1 (M + 1)

516 orange oil 1682.18 356.1 (M + 1)

517 yellow oil 1681.17 340.1 (M + 1)

518 tan oil 1724 377 (M + 2)

519 yellow solid 117-119 323.4 (M + 1)

520 light yellow oil 1683.5 358.1 (M + 1)

521 light yellow oil 1683.77 372.1 (M + 1)

522 1679 372.1 (M + 1)

523 light yellow oil 1678.82 356.1 (M + 1)

524 light yellow oil 1681.3 372.1 (M + 1)

525 thick clear oil 1682 354.1 (M + 1)

526 pale yellow solid 121-125 1678 338 (M + 1)

527 light yellow oil 1660 350.1 (M + 1)

528 light yellow oil 1683 364.1 (M + 1)

529 white solid 82-86 1660 351.1 (M + 1)

530 yellow oil 1686 324.1 (M + 1)

531 brown oil 1684 324.1 (M + 1)

533 orange oil 1688 282.1 (M + 1)

534 orange oil 1671 322.1 (M + 1)

535 brown oil 1675 294.1 (M + 1)

536 yellow solid 144-146 392 (M + 1)

537 light yellow oil 1679.81 386.1 (M + 1)

538 dark oil 1679.94 370.1 (M + 1)

540 yellow oil 1683 406.1 (M + 1)

541 white solid 102-105 1674 405.2 (M + 1)

542 yellow amorphous solid 1668 335.1 (M + 1)

543 yellow amorphous solid 1669 392.1 (M + 1)

544 light yellow oil 1675 359.1 (M + 1)

545 light yellow oil 1657 394.1 (M + 1)

546 brown solid 2977 326 (M + 1)

547 white solid 110-111 1675 415.9 (M + 1)

548 light yellow solid 102-103 1674 432.8 (M + 1)

549 colorless oil 2925 1650 409.9 (M + 1)

550 brown oil 1681 363.9 (M + 1)

551 white solid 92-94 1681 375.9 (M + 1)

552 yellow oil 1675.25 431.9 (M + 1)

553 dark oil 1682.96 321.9 (M + 1)

554 light yellow oil 1645 349.8 (M + 1)

555 light yellow oil 1660 365.0 (M + 1)

556 light yellow oil 1668 365.9 (M + 1)

557 red oil 1683 405.9 (M + 1)

558 white solid 132-135 1684 391.9 (M + 1)

559 pale yellow oil 1674 386 (M + 1)

560 pale yellow oil 1675 402 (M + 1)

561 dark brown oil 1684 392.9 (M + 1)

562 dark brown oil 2926 1681 358.9 (M + 1)

563 light yellow oil 1683 379.9 (M + 1)

564 white solid 172-174 1674 413.8 (M + 1)

565 yellow oil 1673.19 388.0 (M + 2)

566 yellow oil 1669.72 307.98 (M + 1)

567 tan solid 63-68 367.6 (M + 1)

568 clear oil 398 (M + 1)

569 dark oil 1675.09 307.98 (M + 1)

570 yellow solid 118-120 1658 335.1 (M + 1)

571 colorless oil 1669 345.1 (M + 1)

573 yellow oil 1656 334.0 (M + 1)

574 dark brown oil 1669 345.5 (M + 1)

575 yellow oil 1684 394.0 (M + 2)

576 yellow oil 1658 336.0 (M + 2)

577 white solid 115-117 1672 418.0 (M + 2)

578 yellow oil 1659 404.1 (M + 1)

579 yellow solid 46-49 1653 425.5 (M + 1)

580 yellow solid 51-60 435.5 (M + 1)

581 yellow oil 334.5 (M + 1)

582 clear oil 433.5 (M + 1)

583 clear oil 407.4 (M + 1)

584 clear oil 445.4 (M + 1)

585 off-white solid 190-192 434.5 (M + 1)

586 yellow oil 407.4 (M + 1)

587 orange semi- solid 391.5 (M + 1)

588 1681.88 328.05 (M + 1)

589 yellow solid 72-74 326.1 (M + 1), 324.1 (M − 1)

TABLE 2 Biological Results Compound MYZUPE APHIGO BEMITA Number 200 ppm200 ppm 200 ppm 1 B C A 2 B C B 3 B C B 4 B C B 5 C C C 6 B C B 7 B C B8 A C C 9 A C A 10 B C A 11 B C C 12 A C A 13 A C A 14 B C A 15 A C A 16B C A 17 A C A 18 A C A 19 A B B 20 A C A 21 A C A 22 B C B 23 A C B 24A C A 25 A C B 26 B C B 27 A C B 28 A C A 29 A C A 30 A C B 31 A C A 32A C A 33 B C A 34 A C A 35 A C A 36 A C A 37 A C A 38 A C A 39 A C A 40A C A 41 A C A 42 A C A 43 A C A 44 A C A 45 B C A 46 B C B 47 A C A 48A C A 49 B C A 50 A C A 51 A C A 52 B C A 53 B C A 54 A C A 55 A C A 56A C A 57 A C A 58 A C A 59 B C A 60 B C B 61 B C B 62 B C B 63 B C B 64B C B 65 B C B 66 A C A 67 B C B 68 A C A 69 B C A 70 B C B 71 A C C 72A C B 73 A C A 74 A C A 75 A C B 76 A C A 77 A C B 78 A C B 79 A C B 80A C A 81 A C A 82 A C B 83 A C A 84 A C C 85 A C A 86 A C A 87 A C A 88A C A 89 B C A 90 A C A 91 A C A 92 A C B 93 A C B 94 A C B 95 A C A 96A C A 97 A C A 98 A C A 99 A C A 100 A C B 101 A C A 120 C C C 133 A C B134 A C B 135 A C B 136 A C B 137 B C B 138 A C A 139 A C A 140 A C B141 A C A 142 A C B 143 A C B 144 A C B 145 A C B 146 A C B 147 A C B148 A C B 149 B C B 150 A C B 151 B C B 152 B C B 153 B C A 154 B C B155 B C B 156 A C B 157 B C B 158 B C B 159 A C A 160 B C B 161 B C B162 A C A 163 A C B 164 A C B 165 A C A 166 A C A 167 B C A 168 A C A169 B C A 170 B C B 171 A C B 172 A C A 173 A C A 174 A C A 175 B C B176 B C B 177 A C B 178 A C B 179 A C A 180 A C A 181 A C B 182 A C B183 A C A 184 A C A 185 A C A 186 B C B 187 A C B 188 A C A 189 A C A190 A C A 191 A C B 192 A C A 193 A C A 194 A C A 195 A C A 196 A C A197 A C B 198 A C A 199 A C A 200 A C A 201 B C B 202 B C B 203 A C A204 A C B 205 A C A 206 A C A 207 A C A 208 B C B 209 A C B 210 A A A211 A C A 212 A C A 213 A C A 214 A C A 215 A C A 216 A C A 217 A C B218 A A A 219 A C B 220 A C A 221 A C B 222 A C B 223 A C A 224 A C A225 A C A 226 A A A 227 A A A 228 A A A 229 A A B 230 A A A 231 A C A232 B C A 233 A A A 234 A A A 235 A A A 236 A C A 237 A C A 238 A C A239 A C A 240 A A A 241 A A A 242 A B A 243 A A A 244 B B B 245 A A A246 A C A 247 A A A 248 A C A 249 A B A 250 A B B 251 B C A 252 A C A253 A A A 254 A A A 255 A A A 256 A C A 257 A C A 258 A C A 259 A C A260 A C A 261 A C A 262 A A A 263 A C A 264 A C A 265 A C B 266 A C A267 A C A 268 A C A 269 A C A 270 A B A 271 A C A 272 A A A 273 A C A274 A A A 275 A C A 276 A C B 277 A C A 278 A C A 279 A A A 280 B C B281 B C B 282 A C A 283 B C B 284 A C A 285 A C A 286 A C A 287 A C A288 A A A 289 A A A 290 B C B 291 B C B 292 B C A 293 A C B 294 B C B295 B C A 296 A C A 297 B C B 298 A C B 299 A C A 300 A C B 301 A C A302 B C A 303 B C A 304 A C A 305 A C A 306 A C B 307 A C B 308 A C A309 B C B 310 B C C 311 A C C 312 A C A 313 A C A 314 A C A 315 A C A316 A C B 317 A C B 318 A C B 319 A C A 320 A C B 321 A C B 322 A C B323 A C B 324 A C B 325 A C A 326 B C B 327 B C B 328 B C B 329 B C B330 B C B 331 B C A 332 A C B 333 A C B 334 A C B 335 A C A 336 A C A337 B C A 338 C C A 339 B C A 340 A C B 341 B C B 342 B C B 343 A C B344 B C B 345 A C A 346 B C A 347 B C B 348 A C A 349 A C A 350 B C B351 B C B 352 A C B 353 B C A 354 A C A 355 A C B 356 A C A 357 A C A358 A C A 359 A C A 360 A C B 361 A C B 363 B C A 364 A C A 365 A C B366 A C A 367 A C B 368 A C A 369 A C A 370 A C A 371 A C A 372 A C A373 A C A 374 A C A 375 B C B 376 A C A 377 B C A 378 A C A 379 A C B380 B C B 381 B C B 382 B C B 383 B C A 384 A C A 385 A C B 386 A C A387 B C A 388 A C A 389 B C B 390 B C A 391 A C A 392 A C A 393 A C A394 A C A 395 B C B 396 A C A 397 A C A 398 B C A 399 A C A 400 C C C401 A C A 402 A C A 403 A C B 404 A C B 405 A C B 406 A C B 407 A C B408 A C A 409 A C A 410 A C A 411 A C A 412 A C A 413 A C B 414 A C A415 A C A 416 A C A 417 A C A 418 A C A 420 B C A 421 A C B 422 A C B423 B C A 424 A C A 425 A C A 426 A C A 427 A C A 428 B C B 429 A C B430 A C B 431 A C B 432 B C B 433 A C A 434 A C A 435 B C B 436 B C B437 B C B 438 A C B 439 B C B 440 B C B 441 A C A 442 A C A 443 A C A444 A C A 445 A C A 446 A C A 447 A C A 448 A C A 449 A C A 450 A C A451 A C B 452 A C A 453 A C A 454 A C A 455 A C A 456 A C B 457 A C A458 A C A 459 A C B 460 B C B 461 A C B 462 A C B 463 B C B 464 A C B465 A C B 466 A C B 467 A C B 468 A C B 469 A C B 470 A C B 471 A C B472 A C B 473 C C B 474 B C B 475 B C B 476 A C B 477 C C C 478 A C B480 A C A 481 B C B 482 A C A 483 B C A 484 B C A 485 A C A 486 A C B487 A C A 488 A C A 489 A C A 490 A C B 491 A C A 492 B C A 493 A C A494 B C B 495 B C B 496 A C B 497 A C A 498 A C A 499 A C B 500 A C A501 A C A 502 B C B 503 B C B 504 A C A 505 A C A 506 A C B 507 A C A508 B C A 509 A C A 510 A C A 511 A C B 512 B C A 513 B C B 514 B C B515 B C B 516 A C B 517 A C B 518 A C B 519 A C B 520 A C B 521 A C B522 A C B 523 A C B 524 A C A 525 C C C 526 A C A 527 B C A 528 B C A529 A C B 530 A C A 531 A C A 533 A C A 534 B C A 535 B C A 536 B C B537 A C B 538 A C A 540 A C A 541 A C B 542 A C A 543 A C A 544 A C B545 A C B 546 A C A 547 A C A 548 A C A 549 A C A 550 B C A 551 B C B552 A C B 553 B C A 554 B C B 555 A C B 556 A C B 557 B C B 558 B C B559 A C A 560 A C A 561 A C B 562 A C B 563 A C B 564 B C B 565 A C A566 A C A 567 A C B 568 B C B 569 A C A 570 A C B 571 A C B 573 B C B574 A C B 575 A C B 576 A C B 577 A C B 578 A C A 579 A C B 580 B C A581 B C B 582 A C A 583 A C A 584 B C B 585 A C B 586 A C A 587 A C A588 A C A 589 B C B

1. A molecule of formula (“Formula I”):

wherein: (a) X is CR8; (b) R1 is H; (c) R2 is H; (d) R3 is H; (e) R4 isCl; (f) R5 is an unsubstituted C₁-C₆ alkyl; (g) R6 is O; (h) R7 is(unsubstituted C₁-C₆ alkyl)S(O)_(n)(unsubstituted C₁-C₆ alkyl); (i) R8is H or F; and (k) n is 0, 1, or
 2. 2. A molecule according to claim 1having the following structure:


3. A molecule according to claim 1 having the following structure:


4. A molecule according to claim 1 having the following structure:


5. A molecule according to claim 1 in the form of a pesticidallyacceptable acid addition salt, salt derivative, or solvate.
 6. Amolecule according to claim 1 wherein one or more of the hydrogenstherein is ²H.
 7. A molecule according to claim 1 wherein one or more ofthe carbons therein is ¹⁴C.
 8. A molecule according to claim 1 that is aresolved stereoisomer.
 9. A composition comprising a molecule accordingto claim 1 and at least one other compound selected from1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion,acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb,aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin,alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amitonoxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos,azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate,barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin,beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin,biopermethrin, bistrifluron, borax, boric acid, bromfenvinfos,bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb,buprofezin, butacarb, butathiofos, butocarboxim, butonate,butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide,camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbontetrachloride, carbophenothion, carbosulfan, cartap, cartaphydrochloride, chlorantraniliprole, chlorbicyclen, chlordane,chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos,chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform,chloropicrin, chlorphoxim, chlorprazophos, chlorpyrifos,chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerinII, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copperacetoarsenite, copper arsenate, copper naphthenate, copper oleate,coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite,cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclethrin,cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin,cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion,demephion-O, demephion-S, demeton, demeton-methyl, demeton-O,demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon,diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon,dichlofenthion, dichlorvos, dicresyl, dicrotophos, dicyclanil, dieldrin,diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate,dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop,dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion,disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium,DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin,emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin,EPN, epofenonane, eprinomectin, esdepalléthrine, esfenvalerate, etaphos,ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethylformate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethyleneoxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor,fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb,fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion,fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid,flubendiamide (additionally resolved isomers thereof), flucofuron,flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufenprox,fluvalinate, fonofos, formetanate, formetanate hydrochloride,formothion, formparanate, formparanate hydrochloride, fosmethilan,fospirate, fosthietan, furathiocarb, furethrin, gamma-cyhalothrin,gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptenophos,heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide,hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb,iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin,isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate,isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos, juvenilehormone I, juvenile hormone II, juvenile hormone III, kelevan,kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos,lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben,mazidox, mecarbam, mecarphon, menazon, meperfluthrin, mephosfolan,mercurous chloride, mesulfenfos, metaflumizone, methacrifos,methamidophos, methidathion, methiocarb, methocrotophos, methomyl,methoprene, methothrin, methoxychlor, methoxyfenozide, methyl bromide,methyl isothiocyanate, methylchloroform, methylene chloride,metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate,milbemectin, milbemycin oxime, mipafox, mirex, molosultap,monocrotophos, morphothion, moxidectin, naftalofos, naled, naphthalene,nicotine, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron,noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos,oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl,penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin,phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor,phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos,pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite,potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, primidophos, profenofos, profluralin, profluthrin,promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion,prothiofos, prothoate, protrifenbute, pymetrozine, pyraclofos,pyrafluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II,pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon,pyrimidifen, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos,quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania,schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodiumfluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide,spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron,sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfurylfluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide,tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP,terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos,tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiacloprid,thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate,thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium,thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin,transfluthrin, transpermethrin, triarathene, triazamate, triazophos,trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumuron,trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb,zeta-cypermethrin, or zolaprofos.
 10. A composition comprising amolecule according to claim 1 and at least one biopesticide.
 11. Acomposition comprising a molecule according to claim 1 and at least oneof the following compounds: (a)3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;(b)3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;(c) 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone; (d)4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone; (e)3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide;(f) 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide; (g)2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; (h)2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide; (i)2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide; (j)2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide; (k)2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; (l)2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; (m)3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide; (n)N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazone; (o)N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazonenicotine; (p)O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-methylthiocarbonate; (q)(E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;(r)1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol;(s) 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate;or (t)N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha, alpha-trifluoro-p-tolyl)hydrazone.
 12. A compositioncomprising a molecule according to claim 1 and at least one othercompound selected from acequinocyl, amidoflumet, arsenous oxide,azobenzene, azocyclotin, benomyl, benoxafos, benzoximate, benzylbenzoate, bifenazate, binapacryl, bromopropylate, chinomethionat,chlorbenside, chlorfenethol, chlorfenson, chlorfensulphide,chlorobenzilate, chloromebuform, chloromethiuron, chloropropylate,clofentezine, cyenopyrafen, cyflumetofen, cyhexatin, dichlofluanid,dicofol, dienochlor, diflovidazin, dinobuton, dinocap, dinocap-4,dinocap-6, dinocton, dinopenton, dinosulfon, dinoterbon, diphenylsulfone, disulfiram, dofenapyn, etoxazole, fenazaquin, fenbutatin oxide,fenothiocarb, fenpyroximate, fenson, fentrifanil, fluacrypyrim,fluazuron, flubenzimine, fluenetil, flumethrin, fluorbenside,hexythiazox, mesulfen, MNAF, proclonol, propargite, quintiofos,spirodiclofen, sulfiram, sulfur, tetradifon, tetranactin, tetrasul, orthioquinox.
 13. A composition comprising a molecule according to claim 1and at least one other compound selected from 1,3-dichloropropene,benclothiaz, dazomet, dazomet-sodium, DBCP, DCIP, diamidafos,fluensulfone, fosthiazate, furfural, imicyafos, isamidofos, isazofos,metam, metam-ammonium, metam-potassium, metam-sodium, phosphocarb, orthionazin.
 14. A composition comprising a molecule according to claim 1and at least one other compound selected from (3-ethoxypropyl)mercurybromide, 2-methoxyethylmercury chloride, 2-phenylphenol,8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, acibenzolar,acibenzolar-S-methyl, acypetacs, acypetacs-copper, acypetacs-zinc,aldimorph, allyl alcohol, ametoctradin, amisulbrom, ampropylfos,anilazine, aureofungin, azaconazole, azithiram, azoxystrobin, bariumpolysulfide, benalaxyl, benalaxyl-M, benodanil, benomyl, benquinox,bentaluron, benthiavalicarb, benthiavalicarb-isopropyl, benzalkoniumchloride, benzamacril, benzamacril-isobutyl, benzamorf, benzohydroxamicacid, bethoxazin, binapacryl, biphenyl, bitertanol, bithionol, bixafen,blasticidin-S, Bordeaux mixture, boscalid, bromuconazole, bupirimate,Burgundy mixture, buthiobate, butylamine, calcium polysulfide, captafol,captan, carbamorph, carbendazim, carboxin, carpropamid, carvone,Cheshunt mixture, chinomethionat, chlobenthiazone, chloraniformethan,chloranil, chlorfenazole, chloroneb, chloropicrin, chlorothalonil,chlorquinox, chlozolinate, climbazole, clotrimazole, copper acetate,copper carbonate, basic, copper hydroxide, copper naphthenate, copperoleate, copper oxychloride, copper silicate, copper sulfate, copper zincchromate, cresol, cufraneb, cuprobam, cuprous oxide, cyazofamid,cyclafuramid, cycloheximide, cyflufenamid, cymoxanil, cypendazole,cyproconazole, cyprodinil, dazomet, dazomet-sodium, DBCP, debacarb,decafentin, dehydroacetic acid, dichlofluanid, dichlone, dichlorophen,dichlozoline, diclobutrazol, diclocymet, diclomezine,diclomezine-sodium, dicloran, diethofencarb, diethyl pyrocarbonate,difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin,diniconazole, diniconazole-M, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine,dipyrithione, disulfiram, ditalimfos, dithianon, DNOC, DNOC-ammonium,DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorphbenzoate, dodicin, dodicin-sodium, dodine, drazoxolon, edifenphos,epoxiconazole, etaconazole, etem, ethaboxam, ethirimol, ethoxyquin,ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate,ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate,etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenarimol,fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil,fenpropidin, fenpropimorph, fentin, fentin chloride, fentin hydroxide,ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph,fluopicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin,fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil,flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl,fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, furcarbanil,furconazole, furconazole-cis, furfural, furmecyclox, furophanate,glyodin, griseofulvin, guazatine, halacrinate, hexachlorobenzene,hexachlorobutadiene, hexaconazole, hexylthiofos, hydrargaphen,hymexazol, imazalil, imazalil nitrate, imazalil sulfate, imibenconazole,iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate,iodomethane, ipconazole, iprobenfos, iprodione, iprovalicarb,isoprothiolane, isopyrazam, isotianil, isovaledione, kasugamycin,kresoxim-methyl, mancopper, mancozeb, mandipropamid, maneb, mebenil,mecarbinzid, mepanipyrim, mepronil, meptyldinocap, mercuric chloride,mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam,metam-ammonium, metam-potassium, metam-sodium, metazoxolon, metconazole,methasulfocarb, methfuroxam, methyl bromide, methyl isothiocyanate,methylmercury benzoate, methylmercury dicyandiamide, methylmercurypentachlorophenoxide, metiram, metominostrobin, metrafenone,metsulfovax, milneb, myclobutanil, myclozolin,N-(ethylmercury)-p-toluenesulphonanilide, nabam, natamycin,nitrostyrene, nitrothal-isopropyl, nuarimol, OCH, octhilinone, ofurace,orysastrobin, oxadixyl, oxine-copper, oxpoconazole, oxpoconazolefumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen,pentachlorophenol, penthiopyrad, phenylmercuriurea, phenylmercuryacetate, phenylmercury chloride, phenylmercury derivative ofpyrocatechol, phenylmercury nitrate, phenylmercury salicylate,phosdiphen, phthalide, picoxystrobin, piperalin, polycarbamate,polyoxins, polyoxorim, polyoxorim-zinc, potassium azide, potassiumpolysulfide, potassium thiocyanate, probenazole, prochloraz,procymidone, propamocarb, propamocarb hydrochloride, propiconazole,propineb, proquinazid, prothiocarb, prothiocarb hydrochloride,prothioconazole, pyracarbolid, pyraclostrobin, pyraclostrobin,pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril,pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor,pyroxyfur, quinacetol, quinacetol sulfate, quinazamid, quinconazole,quinoxyfen, quintozene, rabenzazole, salicylanilide, sedaxane,silthiofam, simeconazole, sodium azide, sodium orthophenylphenoxide,sodium pentachlorophenoxide, sodium polysulfide, spiroxamine,streptomycin, sulfur, sultropen, tebuconazole, tebufloquin, tecloftalam,tecnazene, tecoram, tetraconazole, thiabendazole, thiadifluor,thicyofen, thifluzamide, thiochlorfenphim, thiomersal, thiophanate,thiophanate-methyl, thioquinox, thiram, tiadinil, tioxymid,tolclofos-methyl, tolylfluanid, tolylmercury acetate, triadimefon,triadimenol, triamiphos, triarimol, triazbutil, triazoxide, tributyltinoxide, trichlamide, tricyclazole, tridemorph, trifloxystrobin,triflumizole, triforine, triticonazole, uniconazole, uniconazole-P,validamycin, valifenalate, vinclozolin, zarilamid, zinc naphthenate,zineb, ziram, or zoxamide.
 15. A composition comprising a moleculeaccording to claim 1 and at least one other compound selected from2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-sodium, 2,4,5-T,2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl,2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl,2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl,2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium,2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl,2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl,2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium,2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium,2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB,2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl,2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium,2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium,2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium,2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium,2,4-D-trolamine, 3,4-DA, 3,4-DB, 3,4-DP, 4-CPA, 4-CPB, 4-CPP,acetochlor, acifluorfen, acifluorfen-methyl, acifluorfen-sodium,aclonifen, acrolein, alachlor, allidochlor, alloxydim, alloxydim-sodium,allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone,amidosulfuron, aminocyclopyrachlor, aminocyclopyrachlor-methyl,aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium,aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl, amitrole,ammonium sulfamate, anilofos, anisuron, asulam, asulam-potassium,asulam-sodium, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne,barban, BCPC, beflubutamid, benazolin, benazolin-dimethylammonium,benazolin-ethyl, benazolin-potassium, bencarbazone, benfluralin,benfuresate, bensulfuron, bensulfuron-methyl, bensulide, bentazone,bentazone-sodium, benzadox, benzadox-ammonium, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzoylprop, benzoylprop-ethyl,benzthiazuron, bicyclopyrone, bifenox, bilanafos, bilanafos-sodium,bispyribac, bispyribac-sodium, borax, bromacil, bromacil-lithium,bromacil-sodium, bromobonil, bromobutide, bromofenoxim, bromoxynil,bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate,bromoxynil-potassium, brompyrazon, butachlor, butafenacil, butamifos,butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon,butylate, cacodylic acid, cafenstrole, calcium chlorate, calciumcyanamide, cambendichlor, carbasulam, carbetamide, carboxazole,carfentrazone, carfentrazone-ethyl, CDEA, CEPC, chlomethoxyfen,chloramben, chloramben-ammonium, chloramben-diolamine,chloramben-methyl, chloramben-methylammonium, chloramben-sodium,chloranocryl, chlorazifop, chlorazifop-propargyl, chlorazine,chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenac-sodium,chlorfenprop, chlorfenprop-methyl, chlorflurazole, chlorflurenol,chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl,chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil,chlorprocarb, chlorpropham, chlorsulfuron, chlorthal,chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, cinidon-ethyl,cinmethylin, cinosulfuron, cisanilide, clethodim, cliodinate,clodinafop, clodinafop-propargyl, clofop, clofop-isobutyl, clomazone,clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,clopyralid-olamine, clopyralid-potassium,clopyralid-tris(2-hydroxypropyl)ammonium, cloransulam,cloransulam-methyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol,cumyluron, cyanamide, cyanatryn, cyanazine, cycloate, cyclosulfamuron,cycloxydim, cycluron, cyhalofop, cyhalofop-butyl, cyperquat, cyperquatchloride, cyprazine, cyprazole, cypromid, daimuron, dalapon,dalapon-calcium, dalapon-magnesium, dalapon-sodium, dazomet,dazomet-sodium, delachlor, desmedipham, desmetryn, di-allate, dicamba,dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium,dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium,dicamba-trolamine, dichlobenil, dichloralurea, dichlormate, dichlorprop,dichlorprop-2-ethylhexyl, dichlorprop-butotyl,dichlorprop-dimethylammonium, dichlorprop-ethylammonium,dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,dichlorprop-P-dimethylammonium, dichlorprop-potassium,dichlorprop-sodium, diclofop, diclofop-methyl, diclosulam, diethamquat,diethamquat dichloride, diethatyl, diethatyl-ethyl, difenopenten,difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate,diflufenican, diflufenzopyr, diflufenzopyr-sodium, dimefuron,dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P,dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam,dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine,dinoseb-sodium, dinoseb-trolamine, dinoterb, dinoterb acetate,diphacinone-sodium, diphenamid, dipropetryn, diquat, diquat dibromide,disul, disul-sodium, dithiopyr, diuron, DMPA, DNOC, DNOC-ammonium,DNOC-potassium, DNOC-sodium, DSMA, EBEP, eglinazine, eglinazine-ethyl,endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium,epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron,ethametsulfuron-methyl, ethidimuron, ethiolate, ethofumesate, ethoxyfen,ethoxyfen-ethyl, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD,fenasulam, fenoprop, fenoprop-3-butoxypropyl, fenoprop-butometyl,fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl,fenoprop-potassium, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P,fenoxaprop-P-ethyl, fenoxasulfone, fenteracol, fenthiaprop,fenthiaprop-ethyl, fentrazamide, fenuron, fenuron TCA, ferrous sulfate,flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl,flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, florasulam,fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P,fluazifop-P-butyl, fluazolate, flucarbazone, flucarbazone-sodium,flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr,flufenpyr-ethyl, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl,flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen,fluoroglycofen-ethyl, fluoromidine, fluoronitrofen, fluothiuron,flupoxam, flupropacil, flupropanate, flupropanate-sodium,flupyrsulfuron, flupyrsulfuron-methyl-sodium, fluridone,flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl,flurtamone, fluthiacet, fluthiacet-methyl, fomesafen, fomesafen-sodium,foramsulfuron, fosamine, fosamine-ammonium, furyloxyfen, glufosinate,glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium,glufosinate-P-sodium, glyphosate, glyphosate-diammonium,glyphosate-dimethylammonium, glyphosate-isopropylammonium,glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium,glyphosate-trimesium, halosafen, halosulfuron, halosulfuron-methyl,haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P,haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium,hexachloroacetone, hexaflurate, hexazinone, imazamethabenz,imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic,imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin,imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr,imazethapyr-ammonium, imazosulfuron, indanofan, indaziflam, iodobonil,iodomethane, iodosulfuron, iodosulfuron-methyl-sodium, ioxynil, ioxyniloctanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipfencarbazone,iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate,isopropalin, isoproturon, isouron, isoxaben, isoxachlortole,isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen,lenacil, linuron, MAA, MAMA, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl,MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl,MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine,MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB,MCPB-ethyl, MCPB-methyl, MCPB-sodium, mecoprop, mecoprop-2-ethylhexyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-isoctyl, mecoprop-methyl, mecoprop-P,mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium,mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medinoterb,medinoterb acetate, mefenacet, mefluidide, mefluidide-diolamine,mefluidide-potassium, mesoprazine, mesosulfuron, mesosulfuron-methyl,mesotrione, metam, metam-ammonium, metamifop, metamitron,metam-potassium, metam-sodium, metazachlor, metazosulfuron, metflurazon,methabenzthiazuron, methalpropalin, methazole, methiobencarb,methiozolin, methiuron, methometon, methoprotryne, methyl bromide,methyl isothiocyanate, methyldymron, metobenzuron, metolachlor,metosulam, metoxuron, metribuzin, metsulfuron, metsulfuron-methyl,molinate, monalide, monisouron, monochloroacetic acid, monolinuron,monuron, monuron TCA, morfamquat, morfamquat dichloride, MSMA,naproanilide, napropamide, naptalam, naptalam-sodium, neburon,nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen,norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene,orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon,oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone,oxyfluorfen, parafluron, paraquat, paraquat dichloride, paraquatdimetilsulfate, pebulate, pelargonic acid, pendimethalin, penoxsulam,pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid,phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron,phenylmercury acetate, picloram, picloram-2-ethylhexyl,picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium,picloram-triethylammonium, picloram-tris(2-hydroxypropyl)ammonium,picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide,potassium cyanate, pretilachlor, primisulfuron, primisulfuron-methyl,procyazine, prodiamine, profluazol, profluralin, profoxydim,proglinazine, proglinazine-ethyl, prometon, prometryn, propachlor,propanil, propaquizafop, propazine, propham, propisochlor,propoxycarbazone, propoxycarbazone-sodium, propyrisulfuron, propyzamide,prosulfalin, prosulfocarb, prosulfuron, proxan, proxan-sodium,prynachlor, pydanon, pyraclonil, pyraflufen, pyraflufen-ethyl,pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazosulfuron-ethyl,pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate,pyriftalid, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrithiobac,pyrithiobac-sodium, pyroxasulfone, pyroxsulam, quinclorac, quinmerac,quinoclamine, quinonamid, quizalofop, quizalofop-ethyl, quizalofop-P,quizalofop-P-ethyl, quizalofop-P-tefuryl, rhodethanil, rimsulfuron,saflufenacil, sebuthylazine, secbumeton, sethoxydim, siduron, simazine,simeton, simetryn, SMA, S-metolachlor, sodium arsenite, sodium azide,sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron,sulfometuron-methyl, sulfosulfuron, sulfuric acid, sulglycapin, swep,TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium,tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim,terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn,tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin,thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron,thifensulfuron-methyl, thiobencarb, tiocarbazil, tioclorim, topramezone,tralkoxydim, tri-allate, triasulfuron, triaziflam, tribenuron,tribenuron-methyl, tricamba, triclopyr, triclopyr-butotyl,triclopyr-ethyl, triclopyr-triethylammonium, tridiphane, trietazine,trifloxysulfuron, trifloxysulfuron-sodium, trifluralin, triflusulfuron,triflusulfuron-methyl, trifop, trifop-methyl, trifopsime,trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron,vernolate, or xylachlor.